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NM_022168.4(IFIH1):c.1764del (p.Ala589fs) AND multiple conditions

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Jun 1, 2022
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
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:
RCV001269324.7

Allele description [Variation Report for NM_022168.4(IFIH1):c.1764del (p.Ala589fs)]

NM_022168.4(IFIH1):c.1764del (p.Ala589fs)

Gene:
IFIH1:interferon induced with helicase C domain 1 [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
2q24.2
Genomic location:
Preferred name:
NM_022168.4(IFIH1):c.1764del (p.Ala589fs)
HGVS:
  • NC_000002.12:g.162278213del
  • NG_011495.1:g.45324del
  • NM_022168.4:c.1764delMANE SELECT
  • NP_071451.2:p.Ala589fs
  • LRG_1235t1:c.1764del
  • LRG_1235:g.45324del
  • LRG_1235p1:p.Ala589fs
  • NC_000002.11:g.163134716del
  • NC_000002.11:g.163134723del
  • NM_022168.3:c.1764del
Protein change:
A589fs
Links:
dbSNP: rs553669430
NCBI 1000 Genomes Browser:
rs553669430
Molecular consequence:
  • NM_022168.4:c.1764del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:
Singleton-Merten syndrome 1 (SGMRT1)
Synonyms:
Widened medullary cavities of bone, aortic calcification, abnormal dentition, and muscular weakness; Syndrome of widened medullary cavities of the metacarpals and phalanges, aortic calcification and abnormal dentition
Identifiers:
MONDO: MONDO:0024535; MedGen: C4225427; Orphanet: 85191; OMIM: 182250
Name:
Aicardi-Goutieres syndrome 7 (AGS7)
Identifiers:
MONDO: MONDO:0014367; MedGen: C3888244; Orphanet: 51; OMIM: 615846

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003514933Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Jun 1, 2022) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

The genomic landscape of pediatric rheumatology disorders in the Middle East.

Fathalla BM, Alsarhan A, Afzal S, El Naofal M, Abou Tayoun A.

Hum Mutat. 2021 Apr;42(4):e1-e14. doi: 10.1002/humu.24165. Epub 2021 Feb 7.

PubMed [citation]
PMID:
33440462
See all PubMed Citations (3)

Details of each submission

From Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital, SCV001448261.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

From Invitae, SCV003514933.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

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. ClinVar contains an entry for this variant (Variation ID: 987915). This premature translational stop signal has been observed in individual(s) with periodic fevers (PMID: 33440462). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change creates a premature translational stop signal (p.Ala589Leufs*16) in the IFIH1 gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in IFIH1 cause disease.

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

Flagged submissions

Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001448261Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital
flagged submission
Reason: This record appears to be redundant with a more recent record from the same submitter.
Notes: SCV001448261 appears to be redundant with SCV002818162.

(ACMG Guidelines, 2015)		Uncertain significance
(Oct 4, 2020) 		germlineclinical testing

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

Last Updated: Jul 7, 2024