8-50449698-G-C

Variant names:

• chr8-50449698-G-C
• rs145093612
• NM_018967.5:c.250G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018967.5(SNTG1):​c.250G>C​(p.Val84Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SNTG1 NM_018967.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0430

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17973626).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNTG1	NM_018967.5	c.250G>C	p.Val84Leu	missense_variant	Exon 6 of 19	ENST00000642720.2	NP_061840.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNTG1	ENST00000642720.2	c.250G>C	p.Val84Leu	missense_variant	Exon 6 of 19		NM_018967.5	ENSP00000493900.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.59
BayesDel_addAF	Benign	-0.031	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	15
DANN	Benign	0.92
DEOGEN2	Benign	0.075	T;T;.;.;.;T;.;.;.;.;.;.
Eigen	Benign	-0.92
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.051	N
LIST_S2	Benign	0.83	.;.;T;T;D;T;T;T;T;T;T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.18	T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.8	L;L;.;.;.;L;.;L;.;.;.;.
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-1.2	N;.;.;.;.;N;.;N;.;N;.;.
REVEL	Benign	0.22
Sift	Uncertain	0.0050	D;.;.;.;.;D;.;D;.;D;.;.
Sift4G	Uncertain	0.0080	D;.;.;.;.;D;.;D;.;D;.;.
Polyphen		0.0060	B;B;.;.;.;B;.;B;.;.;.;.
Vest4		0.65
MutPred		0.61		Gain of catalytic residue at V84 (P = 0.0335);Gain of catalytic residue at V84 (P = 0.0335);.;Gain of catalytic residue at V84 (P = 0.0335);.;Gain of catalytic residue at V84 (P = 0.0335);Gain of catalytic residue at V84 (P = 0.0335);Gain of catalytic residue at V84 (P = 0.0335);Gain of catalytic residue at V84 (P = 0.0335);Gain of catalytic residue at V84 (P = 0.0335);Gain of catalytic residue at V84 (P = 0.0335);Gain of catalytic residue at V84 (P = 0.0335);
MVP		0.60
MPC		0.056
ClinPred		0.58	D
GERP RS		-4.6
Varity_R		0.18
gMVP		0.35

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

Other links and lift over

dbSNP: rs145093612; hg19: chr8-51362258;