8-50502799-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_018967.5(SNTG1):​c.385G>A​(p.Gly129Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000992 in 1,612,378 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

SNTG1
NM_018967.5 missense

Scores

9
6
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.94
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]

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
SNTG1NM_018967.5 linkuse as main transcriptc.385G>A p.Gly129Arg missense_variant 9/19 ENST00000642720.2 NP_061840.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SNTG1ENST00000642720.2 linkuse as main transcriptc.385G>A p.Gly129Arg missense_variant 9/19 NM_018967.5 ENSP00000493900 P1Q9NSN8-1

Frequencies

GnomAD3 genomes
AF:
0.0000526
AC:
8
AN:
152080
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000393
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.000479
GnomAD3 exomes
AF:
0.00000399
AC:
1
AN:
250704
Hom.:
0
AF XY:
0.00000738
AC XY:
1
AN XY:
135546
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000290
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000548
AC:
8
AN:
1460180
Hom.:
0
Cov.:
30
AF XY:
0.00000413
AC XY:
3
AN XY:
726392
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000671
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000663
GnomAD4 genome
AF:
0.0000526
AC:
8
AN:
152198
Hom.:
0
Cov.:
33
AF XY:
0.0000806
AC XY:
6
AN XY:
74404
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.000392
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000474
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.000125
ExAC
AF:
0.00000824
AC:
1

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 GeneticsMay 17, 2023The c.385G>A (p.G129R) alteration is located in exon 9 (coding exon 7) of the SNTG1 gene. This alteration results from a G to A substitution at nucleotide position 385, causing the glycine (G) at amino acid position 129 to be replaced by an arginine (R). 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
0.97
BayesDel_addAF
Pathogenic
0.27
D
BayesDel_noAF
Pathogenic
0.15
CADD
Pathogenic
30
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.13
T;T;.;.;T;.;.;.;.;.;.
Eigen
Pathogenic
0.77
Eigen_PC
Pathogenic
0.74
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Pathogenic
0.98
.;.;D;D;D;D;D;D;D;D;D
M_CAP
Benign
0.027
D
MetaRNN
Uncertain
0.73
D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Benign
-0.53
T
MutationAssessor
Uncertain
2.3
M;M;.;.;M;.;.;M;.;.;.
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Pathogenic
0.90
D
PROVEAN
Pathogenic
-7.2
D;.;.;.;D;.;.;D;.;.;.
REVEL
Uncertain
0.50
Sift
Uncertain
0.0020
D;.;.;.;D;.;.;D;.;.;.
Sift4G
Uncertain
0.0030
D;.;.;.;D;.;.;D;.;.;.
Polyphen
1.0
D;D;.;.;D;.;.;D;.;.;.
Vest4
0.87
MutPred
0.62
Gain of solvent accessibility (P = 0.0306);Gain of solvent accessibility (P = 0.0306);.;.;Gain of solvent accessibility (P = 0.0306);Gain of solvent accessibility (P = 0.0306);.;Gain of solvent accessibility (P = 0.0306);Gain of solvent accessibility (P = 0.0306);Gain of solvent accessibility (P = 0.0306);Gain of solvent accessibility (P = 0.0306);
MVP
0.91
MPC
0.33
ClinPred
1.0
D
GERP RS
4.9
Varity_R
0.79
gMVP
0.70

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs528778271; hg19: chr8-51415359; COSMIC: COSV52459409; API