8-50502836-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018967.5(SNTG1):ā€‹c.422G>Cā€‹(p.Arg141Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000307 in 1,613,240 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 (ā˜…ā˜…).

Frequency

Genomes: š‘“ 0.00027 ( 0 hom., cov: 33)
Exomes š‘“: 0.00031 ( 0 hom. )

Consequence

SNTG1
NM_018967.5 missense

Scores

1
4
14

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 4.94
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.14853075).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SNTG1NM_018967.5 linkuse as main transcriptc.422G>C p.Arg141Thr 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.422G>C p.Arg141Thr missense_variant 9/19 NM_018967.5 ENSP00000493900 P1Q9NSN8-1

Frequencies

GnomAD3 genomes
AF:
0.000270
AC:
41
AN:
152046
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.000588
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000227
AC:
57
AN:
251060
Hom.:
0
AF XY:
0.000236
AC XY:
32
AN XY:
135690
show subpopulations
Gnomad AFR exome
AF:
0.0000616
Gnomad AMR exome
AF:
0.00
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:
0.000485
Gnomad OTH exome
AF:
0.000164
GnomAD4 exome
AF:
0.000311
AC:
454
AN:
1461194
Hom.:
0
Cov.:
30
AF XY:
0.000316
AC XY:
230
AN XY:
726914
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
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:
0.000397
Gnomad4 OTH exome
AF:
0.000199
GnomAD4 genome
AF:
0.000270
AC:
41
AN:
152046
Hom.:
0
Cov.:
33
AF XY:
0.000242
AC XY:
18
AN XY:
74246
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000588
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000410
Hom.:
0
Bravo
AF:
0.000261
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.000778
AC:
3
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.000349
AC:
3
ExAC
AF:
0.000181
AC:
22
EpiCase
AF:
0.000492
EpiControl
AF:
0.000474

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJan 10, 2023The c.422G>C (p.R141T) alteration is located in exon 9 (coding exon 7) of the SNTG1 gene. This alteration results from a G to C substitution at nucleotide position 422, causing the arginine (R) at amino acid position 141 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingRevvity Omics, RevvityOct 14, 2022- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.39
BayesDel_addAF
Benign
-0.31
T
BayesDel_noAF
Benign
-0.35
CADD
Uncertain
24
DANN
Benign
0.93
DEOGEN2
Benign
0.023
T;T;.;.;T;.;.;.;.;.;.
Eigen
Benign
0.17
Eigen_PC
Uncertain
0.30
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.95
.;.;D;D;D;D;D;D;D;D;D
M_CAP
Benign
0.0039
T
MetaRNN
Benign
0.15
T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.1
L;L;.;.;L;.;.;L;.;.;.
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Pathogenic
0.87
D
PROVEAN
Benign
-1.1
N;.;.;.;N;.;.;N;.;.;.
REVEL
Benign
0.16
Sift
Benign
0.41
T;.;.;.;T;.;.;T;.;.;.
Sift4G
Benign
0.26
T;.;.;.;T;.;.;T;.;.;.
Polyphen
0.28
B;B;.;.;B;.;.;B;.;.;.
Vest4
0.55
MVP
0.61
MPC
0.086
ClinPred
0.069
T
GERP RS
4.9
Varity_R
0.33
gMVP
0.35

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: rs141816678; hg19: chr8-51415396; API