chr8-50449693-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_018967.5(SNTG1):ā€‹c.245T>Gā€‹(p.Val82Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000691 in 1,447,468 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 6.9e-7 ( 0 hom. )

Consequence

SNTG1
NM_018967.5 missense

Scores

10
6
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.11
Variant links:
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 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.927

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SNTG1NM_018967.5 linkuse as main transcriptc.245T>G p.Val82Gly missense_variant 6/19 ENST00000642720.2 NP_061840.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SNTG1ENST00000642720.2 linkuse as main transcriptc.245T>G p.Val82Gly missense_variant 6/19 NM_018967.5 ENSP00000493900 P1Q9NSN8-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.91e-7
AC:
1
AN:
1447468
Hom.:
0
Cov.:
29
AF XY:
0.00000139
AC XY:
1
AN XY:
719912
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.06e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

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 submitterclinical testingAmbry GeneticsMar 28, 2024The c.245T>G (p.V82G) alteration is located in exon 6 (coding exon 4) of the SNTG1 gene. This alteration results from a T to G substitution at nucleotide position 245, causing the valine (V) at amino acid position 82 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.98
BayesDel_addAF
Pathogenic
0.27
D
BayesDel_noAF
Pathogenic
0.15
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.16
T;T;.;.;.;T;.;.;.;.;.;.
Eigen
Pathogenic
0.80
Eigen_PC
Pathogenic
0.73
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.94
.;.;D;D;D;D;D;D;D;D;D;D
M_CAP
Benign
0.038
D
MetaRNN
Pathogenic
0.93
D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Uncertain
-0.24
T
MutationAssessor
Pathogenic
3.9
H;H;.;.;.;H;.;H;.;.;.;.
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Uncertain
0.67
T
PROVEAN
Pathogenic
-6.2
D;.;.;.;.;D;.;D;.;D;.;.
REVEL
Uncertain
0.64
Sift
Pathogenic
0.0
D;.;.;.;.;D;.;D;.;D;.;.
Sift4G
Pathogenic
0.0010
D;.;.;.;.;D;.;D;.;D;.;.
Polyphen
0.98
D;D;.;.;.;D;.;D;.;.;.;.
Vest4
0.61
MutPred
0.81
Loss of stability (P = 0.024);Loss of stability (P = 0.024);.;Loss of stability (P = 0.024);.;Loss of stability (P = 0.024);Loss of stability (P = 0.024);Loss of stability (P = 0.024);Loss of stability (P = 0.024);Loss of stability (P = 0.024);Loss of stability (P = 0.024);Loss of stability (P = 0.024);
MVP
0.96
MPC
0.36
ClinPred
1.0
D
GERP RS
5.2
Varity_R
0.94
gMVP
0.80

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-51362253; API