8-50450727-G-C
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Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_018967.5(SNTG1):āc.361G>Cā(p.Val121Leu) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00185 in 1,612,744 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (no stars).
Frequency
Genomes: š 0.0017 ( 1 hom., cov: 33)
Exomes š: 0.0019 ( 0 hom. )
Consequence
SNTG1
NM_018967.5 missense, splice_region
NM_018967.5 missense, splice_region
Scores
4
7
8
Splicing: ADA: 0.8942
1
1
Clinical Significance
Conservation
PhyloP100: 6.58
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 Likely_benign. Variant got -3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.018587768).
BP6
Variant 8-50450727-G-C is Benign according to our data. Variant chr8-50450727-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 3055929.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SNTG1 | NM_018967.5 | c.361G>C | p.Val121Leu | missense_variant, splice_region_variant | 8/19 | ENST00000642720.2 | NP_061840.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SNTG1 | ENST00000642720.2 | c.361G>C | p.Val121Leu | missense_variant, splice_region_variant | 8/19 | NM_018967.5 | ENSP00000493900 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00168 AC: 256AN: 152164Hom.: 1 Cov.: 33
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GnomAD3 exomes AF: 0.00148 AC: 370AN: 250514Hom.: 0 AF XY: 0.00159 AC XY: 215AN XY: 135458
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GnomAD4 exome AF: 0.00187 AC: 2724AN: 1460462Hom.: 0 Cov.: 32 AF XY: 0.00183 AC XY: 1332AN XY: 726568
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GnomAD4 genome AF: 0.00168 AC: 256AN: 152282Hom.: 1 Cov.: 33 AF XY: 0.00161 AC XY: 120AN XY: 74454
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
SNTG1-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 27, 2022 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;T;.;.;.;T;.;.;.;.;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
.;.;D;T;D;D;D;D;D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;.;.;.;M;.;M;.;.;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;.;.;.;.;N;.;N;.;.;.
REVEL
Uncertain
Sift
Uncertain
D;.;.;.;.;D;.;D;.;.;.
Sift4G
Uncertain
D;.;.;.;.;D;.;D;.;.;.
Polyphen
P;P;.;.;.;P;.;D;.;.;.
Vest4
MutPred
Loss of catalytic residue at V121 (P = 0.3687);Loss of catalytic residue at V121 (P = 0.3687);.;Loss of catalytic residue at V121 (P = 0.3687);.;Loss of catalytic residue at V121 (P = 0.3687);Loss of catalytic residue at V121 (P = 0.3687);Loss of catalytic residue at V121 (P = 0.3687);Loss of catalytic residue at V121 (P = 0.3687);Loss of catalytic residue at V121 (P = 0.3687);Loss of catalytic residue at V121 (P = 0.3687);
MVP
MPC
0.20
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
Score
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dbscSNV1_ADA
Benign
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