chr8-50402258-A-C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_018967.5(SNTG1):ā€‹c.76A>Cā€‹(p.Lys26Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000319 in 1,613,276 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā˜…).

Frequency

Genomes: š‘“ 0.0017 ( 1 hom., cov: 32)
Exomes š‘“: 0.00017 ( 1 hom. )

Consequence

SNTG1
NM_018967.5 missense

Scores

5
14

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 6.53
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 Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0095977485).
BP6
Variant 8-50402258-A-C is Benign according to our data. Variant chr8-50402258-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 728154.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SNTG1NM_018967.5 linkuse as main transcriptc.76A>C p.Lys26Gln missense_variant 4/19 ENST00000642720.2 NP_061840.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SNTG1ENST00000642720.2 linkuse as main transcriptc.76A>C p.Lys26Gln missense_variant 4/19 NM_018967.5 ENSP00000493900 P1Q9NSN8-1

Frequencies

GnomAD3 genomes
AF:
0.00172
AC:
261
AN:
152168
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00512
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00295
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:
0.00191
GnomAD3 exomes
AF:
0.000459
AC:
115
AN:
250530
Hom.:
0
AF XY:
0.000295
AC XY:
40
AN XY:
135388
show subpopulations
Gnomad AFR exome
AF:
0.00560
Gnomad AMR exome
AF:
0.000552
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:
0.00000881
Gnomad OTH exome
AF:
0.000654
GnomAD4 exome
AF:
0.000173
AC:
253
AN:
1460990
Hom.:
1
Cov.:
33
AF XY:
0.000138
AC XY:
100
AN XY:
726774
show subpopulations
Gnomad4 AFR exome
AF:
0.00500
Gnomad4 AMR exome
AF:
0.000719
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:
0.0000153
Gnomad4 OTH exome
AF:
0.000596
GnomAD4 genome
AF:
0.00171
AC:
261
AN:
152286
Hom.:
1
Cov.:
32
AF XY:
0.00173
AC XY:
129
AN XY:
74470
show subpopulations
Gnomad4 AFR
AF:
0.00510
Gnomad4 AMR
AF:
0.00294
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:
0.00189
Alfa
AF:
0.000351
Hom.:
0
Bravo
AF:
0.00229
ESP6500AA
AF:
0.00431
AC:
19
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.000494
AC:
60
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

SNTG1-related disorder Benign:1
Likely benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesMay 02, 2019This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpMay 21, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Benign
-0.43
T
BayesDel_noAF
Benign
-0.39
CADD
Benign
23
DANN
Benign
0.95
DEOGEN2
Benign
0.017
T;T;.;.;T;.;.;.;.;.;.;.
Eigen
Uncertain
0.23
Eigen_PC
Uncertain
0.32
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Uncertain
0.93
.;.;D;D;D;D;D;D;D;D;D;D
M_CAP
Benign
0.0025
T
MetaRNN
Benign
0.0096
T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.6
L;L;.;.;L;.;.;L;.;.;.;.
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Uncertain
0.60
T
PROVEAN
Benign
-0.43
N;.;.;.;N;.;.;N;.;N;.;.
REVEL
Benign
0.13
Sift
Benign
0.35
T;.;.;.;T;.;.;T;.;T;.;.
Sift4G
Benign
0.53
T;.;.;.;T;.;.;T;.;T;.;.
Polyphen
0.76
P;P;.;.;P;.;.;P;.;.;.;.
Vest4
0.50
MVP
0.61
MPC
0.065
ClinPred
0.046
T
GERP RS
5.0
Varity_R
0.24
gMVP
0.29

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: rs35384568; hg19: chr8-51314818; API