rs1556889524
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1PM2PP2
The NM_006306.4(SMC1A):c.2038C>T(p.Arg680Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,098,057 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R680H) has been classified as Likely benign.
Frequency
Consequence
NM_006306.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SMC1A | NM_006306.4 | c.2038C>T | p.Arg680Cys | missense_variant | 12/25 | ENST00000322213.9 | |
SMC1A | NM_001281463.1 | c.1972C>T | p.Arg658Cys | missense_variant | 13/26 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMC1A | ENST00000322213.9 | c.2038C>T | p.Arg680Cys | missense_variant | 12/25 | 1 | NM_006306.4 | P1 |
Frequencies
GnomAD3 genomes Cov.: 23
GnomAD4 exome AF: 9.11e-7 AC: 1AN: 1098057Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 363421
GnomAD4 genome Cov.: 23
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 30, 2019 | The c.2038C>T (p.R680C) alteration is located in coding exon 12 of the SMC1A gene. This alteration results from a C to T substitution at nucleotide position 2038, causing the arginine (R) at amino acid position 680 to be replaced by a cysteine (C). The alteration is not observed in population databases:_x000D_ _x000D_ Based on data from the NHLBI Exome Sequencing Project (ESP), the SMC1A c.2038C>T alteration was not observed among 6,503 individuals tested. Allele frequency data for this nucleotide position are not currently available from the 1000 Genomes Project or ExAC and the alteration is not currently listed in the Database of Single Nucleotide Polymorphisms (dbSNP). Rare missense alleles commonly exhibit a deleterious effect on protein function (Kryukov, 2007; Tennessen, 2012; please note that some variants may appear to be rare due to ethnic underrepresentation in the database)._x000D_ _x000D_ _x000D_ Kryukov GV, et al. (2007) Am J Hum Genet 80:727-739._x000D_ _x000D_ Tennessen JA, et al. (2012) Science 337(64):64-69. The altered amino acid is conserved throughout evolution:_x000D_ _x000D_ The p.R680 amino acid is conserved through available mammal species. The alteration is predicted deleterious by in silico models:_x000D_ _x000D_ The p.R680C alteration is predicted to be possibly damaging by Polyphen and deleterious by SIFT in silico analyses. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at