Variant 2-1098209-C-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_018968.4(SNTG2):c.224C>A(p.Thr75Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,700 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

SNTG2
NM_018968.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.42

Variant links:

Genes affected

SNTG2 (HGNC:13741): (syntrophin gamma 2) This gene encodes a protein belonging to the syntrophin family. Syntrophins are cytoplasmic peripheral membrane proteins that bind to components of mechanosenstive sodium channels and the extreme carboxy-terminal domain of dystrophin and dystrophin-related proteins. The PDZ domain of this protein product interacts with a protein component of a mechanosensitive sodium channel that affects channel gating. Absence or reduction of this protein product has been associated with Duchenne muscular dystrophy. There is evidence of alternative splicing yet the full-length nature of these variants has not been described. [provided by RefSeq, Jul 2008]

SNTG2 links:

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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=0.17181632).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNTG2	NM_018968.4 linkuse as main transcript	c.224C>A	p.Thr75Lys	missense_variant	3/17	ENST00000308624.10	NP_061841.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNTG2	ENST00000308624.10 linkuse as main transcript	c.224C>A	p.Thr75Lys	missense_variant	3/17	1	NM_018968.4	ENSP00000311837	P1	Q9NY99-1
SNTG2	ENST00000407292.1 linkuse as main transcript	c.210+14554C>A		intron_variant		1		ENSP00000385020		Q9NY99-2
SNTG2	ENST00000450962.5 linkuse as main transcript	c.224C>A	p.Thr75Lys	missense_variant, NMD_transcript_variant	3/8	5		ENSP00000401997
SNTG2	ENST00000452177.5 linkuse as main transcript	c.224C>A	p.Thr75Lys	missense_variant, NMD_transcript_variant	3/8	2		ENSP00000412249

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000802

AC:

AN:

249258

Hom.:

AF XY:

0.00000740

AC XY:

AN XY:

135220

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:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461700

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727130

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:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000828

AC:

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

May 26, 2022

The c.224C>A (p.T75K) alteration is located in exon 3 (coding exon 3) of the SNTG2 gene. This alteration results from a C to A substitution at nucleotide position 224, causing the threonine (T) at amino acid position 75 to be replaced by a lysine (K). 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

Benign

0.12

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.75

DEOGEN2

Benign

0.014

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.76

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.014

MetaRNN

Benign

0.17

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.23

MutationTaster

Benign

1.0

D;N

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-2.1

REVEL

Benign

0.11

Sift

Benign

0.36

Sift4G

Benign

0.99

Polyphen

0.016

Vest4

0.53

MutPred

0.57

Loss of phosphorylation at T75 (P = 0.0123);

MVP

0.14

MPC

0.13

ClinPred

0.084

GERP RS

3.8

Varity_R

0.070

gMVP

0.52

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over