7-66995377-T-C
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1PP3_StrongPP5_Moderate
The NM_016038.4(SBDS):c.41A>G(p.Asn14Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000547 in 1,461,758 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N14Y) has been classified as Uncertain significance.
Frequency
Consequence
NM_016038.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SBDS | NM_016038.4 | c.41A>G | p.Asn14Ser | missense_variant | 1/5 | ENST00000246868.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SBDS | ENST00000246868.7 | c.41A>G | p.Asn14Ser | missense_variant | 1/5 | 1 | NM_016038.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251458Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135920
GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461758Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4AN XY: 727190
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | GeneDx | May 19, 2015 | The N14S variant in the SBDS gene has not been published as a pathogenic variant, nor has it been reported as a benign polymorphism to our knowledge. It was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The N14S variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is not well conserved across species. However, missense variants in nearby residues (P6L, N8K, T13N, and R19Q) have been reported in the Human Gene Mutation Database in association with Shwachman-Diamond syndrome (Stenson et al., 2014), supporting the functional importance of this region of the protein. In silico analysis predicts this variant is probably damaging to the protein structure/function. The N14S variant is a strong candidate for a disease-causing variant, however the possibility it may be a rare benign variant cannot be excluded - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at