8-50530233-C-T
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_018967.5(SNTG1):c.523C>T(p.His175Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Consequence
SNTG1
NM_018967.5 missense
NM_018967.5 missense
Scores
2
12
5
Clinical Significance
Conservation
PhyloP100: 6.77
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]
Genome browser will be placed here
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.523C>T | p.His175Tyr | missense_variant | 10/19 | ENST00000642720.2 | NP_061840.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SNTG1 | ENST00000642720.2 | c.523C>T | p.His175Tyr | missense_variant | 10/19 | NM_018967.5 | ENSP00000493900 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 30
GnomAD4 exome
Cov.:
30
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
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 | Oct 12, 2022 | The c.523C>T (p.H175Y) alteration is located in exon 10 (coding exon 8) of the SNTG1 gene. This alteration results from a C to T substitution at nucleotide position 523, causing the histidine (H) at amino acid position 175 to be replaced by a tyrosine (Y). 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
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T;.;.;T;.;.;.;.;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
.;.;D;D;D;D;D;D;D;D;D
M_CAP
Benign
T
MetaRNN
Uncertain
D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;.;.;M;.;.;M;.;.;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D;.;.;.;D;.;.;D;.;.;.
REVEL
Benign
Sift
Uncertain
D;.;.;.;D;.;.;D;.;.;.
Sift4G
Uncertain
D;.;.;.;D;.;.;D;.;.;.
Polyphen
P;P;.;.;P;.;.;D;.;.;.
Vest4
MutPred
Gain of phosphorylation at H175 (P = 0.0921);Gain of phosphorylation at H175 (P = 0.0921);.;.;Gain of phosphorylation at H175 (P = 0.0921);Gain of phosphorylation at H175 (P = 0.0921);.;Gain of phosphorylation at H175 (P = 0.0921);Gain of phosphorylation at H175 (P = 0.0921);Gain of phosphorylation at H175 (P = 0.0921);Gain of phosphorylation at H175 (P = 0.0921);
MVP
MPC
0.29
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at