chr8-50402265-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_018967.5(SNTG1):c.83G>A(p.Arg28Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000198 in 1,613,338 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 Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000020 ( 0 hom. )
Consequence
SNTG1
NM_018967.5 missense
NM_018967.5 missense
Scores
3
9
7
Clinical Significance
Conservation
PhyloP100: 8.90
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 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.40119833).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SNTG1 | NM_018967.5 | c.83G>A | p.Arg28Gln | missense_variant | 4/19 | ENST00000642720.2 | NP_061840.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SNTG1 | ENST00000642720.2 | c.83G>A | p.Arg28Gln | missense_variant | 4/19 | NM_018967.5 | ENSP00000493900 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 151980Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000677 AC: 17AN: 250942Hom.: 0 AF XY: 0.0000664 AC XY: 9AN XY: 135632
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GnomAD4 exome AF: 0.0000198 AC: 29AN: 1461358Hom.: 0 Cov.: 33 AF XY: 0.0000206 AC XY: 15AN XY: 726992
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 151980Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74250
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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 | Oct 05, 2023 | The c.83G>A (p.R28Q) alteration is located in exon 4 (coding exon 2) of the SNTG1 gene. This alteration results from a G to A substitution at nucleotide position 83, causing the arginine (R) at amino acid position 28 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T;T;.;.;T;.;.;.;.;.;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
.;.;D;D;D;D;D;D;D;D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;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
T
PROVEAN
Uncertain
D;.;.;.;D;.;.;D;.;D;.;.
REVEL
Benign
Sift
Uncertain
D;.;.;.;D;.;.;D;.;D;.;.
Sift4G
Uncertain
D;.;.;.;D;.;.;D;.;D;.;.
Polyphen
P;P;.;.;P;.;.;D;.;.;.;.
Vest4
MutPred
Loss of catalytic residue at R28 (P = 0.0447);Loss of catalytic residue at R28 (P = 0.0447);Loss of catalytic residue at R28 (P = 0.0447);Loss of catalytic residue at R28 (P = 0.0447);Loss of catalytic residue at R28 (P = 0.0447);Loss of catalytic residue at R28 (P = 0.0447);Loss of catalytic residue at R28 (P = 0.0447);Loss of catalytic residue at R28 (P = 0.0447);Loss of catalytic residue at R28 (P = 0.0447);Loss of catalytic residue at R28 (P = 0.0447);Loss of catalytic residue at R28 (P = 0.0447);Loss of catalytic residue at R28 (P = 0.0447);
MVP
MPC
0.21
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at