chr7-66995311-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM1PP3BP4
The NM_016038.4(SBDS):āc.107T>Cā(p.Val36Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00016 in 1,613,932 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_016038.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SBDS | NM_016038.4 | c.107T>C | p.Val36Ala | missense_variant | Exon 1 of 5 | ENST00000246868.7 | NP_057122.2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000158 AC: 24AN: 152178Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000155 AC: 39AN: 251424Hom.: 0 AF XY: 0.000147 AC XY: 20AN XY: 135914
GnomAD4 exome AF: 0.000160 AC: 234AN: 1461636Hom.: 0 Cov.: 31 AF XY: 0.000149 AC XY: 108AN XY: 727110
GnomAD4 genome AF: 0.000158 AC: 24AN: 152296Hom.: 0 Cov.: 33 AF XY: 0.000148 AC XY: 11AN XY: 74474
ClinVar
Submissions by phenotype
not specified Uncertain:1
DNA sequence analysis of the SBDS gene demonstrated a sequence change, c.107T>C, in exon 1 that results in an amino acid change, p.Val36Ala. This sequence change does not appear to have been previously described in patients with SBDS-related disorders and has been described in the gnomAD database with a low population frequency of 0.014% (dbSNP rs548436732). The p.Val36Ala change affects a highly conserved amino acid residue located in a domain of the SBDS protein that is known to be functional. In-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL) provide contradictory results for the p.Val36Ala substitution. Due to these contrasting evidences and the lack of functional studies, the clinical significance of the p.Val36Ala change remains unknown at this time. -
SBDS-related disorder Uncertain:1
The SBDS c.107T>C variant is predicted to result in the amino acid substitution p.Val36Ala. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.040% of alleles in individuals of Latino descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at