Variant chr8-50530239-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_018967.5(SNTG1):c.529A>T(p.Asn177Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,460,932 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 (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

SNTG1
NM_018967.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.98

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]

SNTG1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.755

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNTG1	NM_018967.5 link	c.529A>T	p.Asn177Tyr	missense_variant	10/19	ENST00000642720.2	NP_061840.1	Q9NSN8-1A0A024R7Y0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNTG1	ENST00000642720.2 link	c.529A>T	p.Asn177Tyr	missense_variant	10/19		NM_018967.5	ENSP00000493900.1		Q9NSN8-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1460932

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726778

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:

0.00000450

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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 submitter

clinical testing

Ambry Genetics

Mar 19, 2024

The c.529A>T (p.N177Y) alteration is located in exon 10 (coding exon 8) of the SNTG1 gene. This alteration results from a A to T substitution at nucleotide position 529, causing the asparagine (N) at amino acid position 177 to be replaced by a tyrosine (Y). 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

0.78

BayesDel_addAF

Pathogenic

0.22

BayesDel_noAF

Uncertain

0.070

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

T;T;.;.;T;.;.;.;.;.;.

Eigen

Pathogenic

0.76

Eigen_PC

Pathogenic

0.75

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.97

.;.;D;D;D;D;D;D;D;D;D

M_CAP

Benign

0.016

MetaRNN

Pathogenic

0.75

D;D;D;D;D;D;D;D;D;D;D

MetaSVM

Benign

-0.84

MutationAssessor

Benign

1.8

L;L;.;.;L;.;.;L;.;.;.

PrimateAI

Pathogenic

0.88

PROVEAN

Pathogenic

-5.0

D;.;.;.;D;.;.;D;.;.;.

REVEL

Uncertain

0.45

Sift

Benign

0.039

D;.;.;.;D;.;.;D;.;.;.

Sift4G

Uncertain

0.0080

D;.;.;.;D;.;.;D;.;.;.

Polyphen

0.99

D;D;.;.;D;.;.;D;.;.;.

Vest4

0.92

MutPred

0.34

Loss of disorder (P = 0.0833);Loss of disorder (P = 0.0833);.;.;Loss of disorder (P = 0.0833);Loss of disorder (P = 0.0833);.;Loss of disorder (P = 0.0833);Loss of disorder (P = 0.0833);Loss of disorder (P = 0.0833);Loss of disorder (P = 0.0833);

MVP

0.92

MPC

0.31

ClinPred

1.0

GERP RS

5.7

Varity_R

0.52

gMVP

0.52

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over