16-51137149-C-T
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_002968.3(SALL1):c.3938G>A(p.Arg1313His) variant causes a missense change. The variant allele was found at a frequency of 0.0000173 in 1,614,156 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1313C) has been classified as Uncertain significance.
Frequency
Consequence
NM_002968.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SALL1 | NM_002968.3 | c.3938G>A | p.Arg1313His | missense_variant | 3/3 | ENST00000251020.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SALL1 | ENST00000251020.9 | c.3938G>A | p.Arg1313His | missense_variant | 3/3 | 1 | NM_002968.3 | P2 |
Frequencies
GnomAD3 genomes AF: 0.0000657 AC: 10AN: 152152Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000676 AC: 17AN: 251458Hom.: 0 AF XY: 0.0000589 AC XY: 8AN XY: 135912
GnomAD4 exome AF: 0.0000123 AC: 18AN: 1461886Hom.: 0 Cov.: 30 AF XY: 0.0000124 AC XY: 9AN XY: 727248
GnomAD4 genome AF: 0.0000657 AC: 10AN: 152270Hom.: 0 Cov.: 31 AF XY: 0.0000403 AC XY: 3AN XY: 74456
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 12, 2022 | The c.3938G>A (p.R1313H) alteration is located in exon 3 (coding exon 3) of the SALL1 gene. This alteration results from a G to A substitution at nucleotide position 3938, causing the arginine (R) at amino acid position 1313 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Townes syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 01, 2023 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 426902). This variant has not been reported in the literature in individuals affected with SALL1-related conditions. This variant is present in population databases (rs529030284, gnomAD 0.06%), and has an allele count higher than expected for a pathogenic variant. This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 1313 of the SALL1 protein (p.Arg1313His). - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 15, 2021 | This variant is associated with the following publications: (PMID: 26257827) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at