chr8-50530233-C-T

Position:

• chr8-50530233-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_018967.5(SNTG1):​c.523C>T​(p.His175Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SNTG1 NM_018967.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.77

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNTG1	NM_018967.5	c.523C>T	p.His175Tyr	missense_variant	10/19	ENST00000642720.2	NP_061840.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNTG1	ENST00000642720.2	c.523C>T	p.His175Tyr	missense_variant	10/19		NM_018967.5	ENSP00000493900	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 12, 2022

The c.523C>T (p.H175Y) alteration is located in exon 10 (coding exon 8) of the SNTG1 gene. This alteration results from a C to T substitution at nucleotide position 523, causing the histidine (H) at amino acid position 175 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	0.74
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T;T;.;.;T;.;.;.;.;.;.
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.97	.;.;D;D;D;D;D;D;D;D;D
M_CAP	Benign	0.0098	T
MetaRNN	Uncertain	0.56	D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.2	M;M;.;.;M;.;.;M;.;.;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Pathogenic	0.86	D
PROVEAN	Uncertain	-3.8	D;.;.;.;D;.;.;D;.;.;.
REVEL	Benign	0.25
Sift	Uncertain	0.014	D;.;.;.;D;.;.;D;.;.;.
Sift4G	Uncertain	0.035	D;.;.;.;D;.;.;D;.;.;.
Polyphen		0.85	P;P;.;.;P;.;.;D;.;.;.
Vest4		0.79
MutPred		0.31		Gain of phosphorylation at H175 (P = 0.0921);Gain of phosphorylation at H175 (P = 0.0921);.;.;Gain of phosphorylation at H175 (P = 0.0921);Gain of phosphorylation at H175 (P = 0.0921);.;Gain of phosphorylation at H175 (P = 0.0921);Gain of phosphorylation at H175 (P = 0.0921);Gain of phosphorylation at H175 (P = 0.0921);Gain of phosphorylation at H175 (P = 0.0921);
MVP		0.86
MPC		0.29
ClinPred		0.99	D
GERP RS		5.7
Varity_R		0.53
gMVP		0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		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

Other links and lift over

dbSNP: rs2094255723; hg19: chr8-51442793; COSMIC: COSV52423126;