chr8-50449698-G-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_018967.5(SNTG1):​c.250G>A​(p.Val84Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00228 in 1,594,966 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0024 ( 19 hom. )

Consequence

SNTG1
NM_018967.5 missense

Scores

19

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.0430
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 Benign. Variant got -9 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.008958966).
BP6
Variant 8-50449698-G-A is Benign according to our data. Variant chr8-50449698-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3050595.Status of the report is no_assertion_criteria_provided, 0 stars.
BS2
High Homozygotes in GnomAdExome4 at 19 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SNTG1NM_018967.5 linkuse as main transcriptc.250G>A p.Val84Ile 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.250G>A p.Val84Ile missense_variant 6/19 NM_018967.5 ENSP00000493900 P1Q9NSN8-1

Frequencies

GnomAD3 genomes
AF:
0.00136
AC:
207
AN:
152062
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00118
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00226
Gnomad OTH
AF:
0.00240
GnomAD3 exomes
AF:
0.00136
AC:
335
AN:
245820
Hom.:
2
AF XY:
0.00151
AC XY:
201
AN XY:
133012
show subpopulations
Gnomad AFR exome
AF:
0.000378
Gnomad AMR exome
AF:
0.000941
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00134
Gnomad FIN exome
AF:
0.0000463
Gnomad NFE exome
AF:
0.00219
Gnomad OTH exome
AF:
0.00203
GnomAD4 exome
AF:
0.00238
AC:
3429
AN:
1442786
Hom.:
19
Cov.:
29
AF XY:
0.00237
AC XY:
1704
AN XY:
717518
show subpopulations
Gnomad4 AFR exome
AF:
0.000303
Gnomad4 AMR exome
AF:
0.00126
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00139
Gnomad4 FIN exome
AF:
0.000133
Gnomad4 NFE exome
AF:
0.00284
Gnomad4 OTH exome
AF:
0.00198
GnomAD4 genome
AF:
0.00135
AC:
206
AN:
152180
Hom.:
0
Cov.:
33
AF XY:
0.00124
AC XY:
92
AN XY:
74408
show subpopulations
Gnomad4 AFR
AF:
0.000482
Gnomad4 AMR
AF:
0.00111
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00208
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00226
Gnomad4 OTH
AF:
0.00237
Alfa
AF:
0.00207
Hom.:
1
Bravo
AF:
0.00146
TwinsUK
AF:
0.00243
AC:
9
ALSPAC
AF:
0.00311
AC:
12
ESP6500AA
AF:
0.000454
AC:
2
ESP6500EA
AF:
0.00337
AC:
29
ExAC
AF:
0.00137
AC:
166
Asia WGS
AF:
0.000577
AC:
2
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

SNTG1-related disorder Benign:1
Likely benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesNov 10, 2020This 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). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.046
BayesDel_addAF
Benign
-0.55
T
BayesDel_noAF
Benign
-0.56
CADD
Benign
4.4
DANN
Benign
0.38
DEOGEN2
Benign
0.021
T;T;.;.;.;T;.;.;.;.;.;.
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.0054
N
LIST_S2
Benign
0.82
.;.;T;T;T;T;T;T;T;T;T;T
M_CAP
Benign
0.0023
T
MetaRNN
Benign
0.0090
T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
-0.79
N;N;.;.;.;N;.;N;.;.;.;.
MutationTaster
Benign
1.0
N;N;N;N
PrimateAI
Benign
0.47
T
PROVEAN
Benign
0.60
N;.;.;.;.;N;.;N;.;N;.;.
REVEL
Benign
0.11
Sift
Benign
1.0
T;.;.;.;.;T;.;T;.;T;.;.
Sift4G
Benign
1.0
T;.;.;.;.;T;.;T;.;T;.;.
Polyphen
0.0
B;B;.;.;.;B;.;B;.;.;.;.
Vest4
0.22
MVP
0.26
MPC
0.046
ClinPred
0.0012
T
GERP RS
-4.6
Varity_R
0.019
gMVP
0.11

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: rs145093612; hg19: chr8-51362258; COSMIC: COSV99386967; API