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NM_001378454.1(ALMS1):c.12103G>A (p.Ala4035Thr) AND Alstrom syndrome

Germline classification:
Conflicting interpretations of pathogenicity (3 submissions)
Last evaluated:
Jun 23, 2022
Review status:
criteria provided, conflicting classifications
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV001833728.5

Allele description [Variation Report for NM_001378454.1(ALMS1):c.12103G>A (p.Ala4035Thr)]

NM_001378454.1(ALMS1):c.12103G>A (p.Ala4035Thr)

Genes:
ALMS1:ALMS1 centrosome and basal body associated protein [Gene - OMIM - HGNC]
LOC126806252:BRD4-independent group 4 enhancer GRCh37_chr2:73828496-73829695 [Gene]
Variant type:
single nucleotide variant
Cytogenetic location:
2p13.1
Genomic location:
Preferred name:
NM_001378454.1(ALMS1):c.12103G>A (p.Ala4035Thr)
HGVS:
  • NC_000002.12:g.73601425G>A
  • NG_011690.1:g.220673G>A
  • NM_001378454.1:c.12103G>AMANE SELECT
  • NM_015120.4:c.12106G>A
  • NP_001365383.1:p.Ala4035Thr
  • NP_055935.4:p.Ala4036Thr
  • LRG_741t1:c.12106G>A
  • LRG_741:g.220673G>A
  • LRG_741p1:p.Ala4036Thr
  • NC_000002.11:g.73828552G>A
  • NC_000002.11:g.73828552G>A
Protein change:
A4035T
Links:
dbSNP: rs757364858
NCBI 1000 Genomes Browser:
rs757364858
Molecular consequence:
  • NM_001378454.1:c.12103G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_015120.4:c.12106G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Alstrom syndrome (ALMS)
Synonyms:
Alstrom's syndrome
Identifiers:
MONDO: MONDO:0008763; MedGen: C0268425; Orphanet: 64; OMIM: 203800

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV002079052Natera, Inc.
no assertion criteria provided
Uncertain significance
(Jul 21, 2021)
germlineclinical testing

SCV002162039Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Uncertain significance
(Jun 23, 2022)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

SCV003928180Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic
criteria provided, single submitter

(K & H Uppaluri Personalized Medicine Clinic Variant Classification & Assertion Criteria_Updated V.1)
Likely risk alleleunknownresearch

PubMed (4)
[See all records that cite these PMIDs]

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedunknownunknownnot providednot providednot providednot providednot providedresearch

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Novel Mutations of the ALMS1 Gene in Patients with Alström Syndrome.

Wang C, Luo X, Wang Y, Liu Z, Wu S, Wang S, Lan X, Xu Q, Xu W, Yuan F, Wang A, Zeng F, Jia J, Chen Y.

Intern Med. 2021 Dec 1;60(23):3721-3728. doi: 10.2169/internalmedicine.6467-20. Epub 2021 Jun 19.

PubMed [citation]
PMID:
34148947
PMCID:
PMC8710367
See all PubMed Citations (5)

Details of each submission

From Natera, Inc., SCV002079052.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Invitae, SCV002162039.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 4036 of the ALMS1 protein (p.Ala4036Thr). This variant is present in population databases (rs757364858, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with ALMS1-related conditions. ClinVar contains an entry for this variant (Variation ID: 916711). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic, SCV003928180.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providedresearch PubMed (4)

Description

Potent mutations in ALMS1 are associated with a rare condition called Alstrom syndrome. It can cause excessive eating, insulin resistance. However, no evidence is found to ascertain the role of rs757364858 in Alstrom syndrome yet.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Feb 4, 2024