8-50450556-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_018967.5(SNTG1):c.278C>T(p.Ala93Val) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000589 in 1,613,198 control chromosomes in the GnomAD database, with no homozygous occurrence. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000059 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000059 ( 0 hom. )
Consequence
SNTG1
NM_018967.5 missense, splice_region
NM_018967.5 missense, splice_region
Scores
4
11
4
Splicing: ADA: 0.9957
2
Clinical Significance
Conservation
PhyloP100: 5.22
Genes affected
SNTG1 (HGNC:13740): (syntrophin gamma 1) The protein encoded by this gene is a member of the syntrophin family. Syntrophins are cytoplasmic peripheral membrane proteins that typically contain 2 pleckstrin homology (PH) domains, a PDZ domain that bisects the first PH domain, and a C-terminal domain that mediates dystrophin binding. This family member plays a role in mediating gamma-enolase trafficking to the plasma membrane and in enhancing its neurotrophic activity. Mutations in this gene are associated with idiopathic scoliosis. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Mar 2016]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SNTG1 | NM_018967.5 | c.278C>T | p.Ala93Val | missense_variant, splice_region_variant | 7/19 | ENST00000642720.2 | NP_061840.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SNTG1 | ENST00000642720.2 | c.278C>T | p.Ala93Val | missense_variant, splice_region_variant | 7/19 | NM_018967.5 | ENSP00000493900 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000592 AC: 9AN: 152114Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000876 AC: 22AN: 251060Hom.: 0 AF XY: 0.000111 AC XY: 15AN XY: 135698
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GnomAD4 exome AF: 0.0000589 AC: 86AN: 1460966Hom.: 0 Cov.: 32 AF XY: 0.0000592 AC XY: 43AN XY: 726826
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GnomAD4 genome AF: 0.0000591 AC: 9AN: 152232Hom.: 0 Cov.: 33 AF XY: 0.0000537 AC XY: 4AN XY: 74440
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 15, 2023 | The c.278C>T (p.A93V) alteration is located in exon 7 (coding exon 5) of the SNTG1 gene. This alteration results from a C to T substitution at nucleotide position 278, causing the alanine (A) at amino acid position 93 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T;.;.;.;T;.;.;.;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
.;.;T;T;T;T;T;T;T;T;T
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
M;M;.;.;.;M;.;M;.;.;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;.;.;.;.;D;.;D;.;.;.
REVEL
Uncertain
Sift
Uncertain
D;.;.;.;.;D;.;D;.;.;.
Sift4G
Pathogenic
D;.;.;.;.;D;.;D;.;.;.
Polyphen
P;P;.;.;.;P;.;D;.;.;.
Vest4
MVP
MPC
0.35
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Pathogenic
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at