8-50449693-T-G

Position:

• chr8-50449693-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_018967.5(SNTG1):​c.245T>G​(p.Val82Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000691 in 1,447,468 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: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SNTG1 NM_018967.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.11

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.927

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNTG1	NM_018967.5	c.245T>G	p.Val82Gly	missense_variant	6/19	ENST00000642720.2	NP_061840.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNTG1	ENST00000642720.2	c.245T>G	p.Val82Gly	missense_variant	6/19		NM_018967.5	ENSP00000493900	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.91e-7 AC: 1 AN: 1447468 Hom.: 0 Cov.: 29 AF XY: 0.00000139 AC XY: 1 AN XY: 719912

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: 9.06e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

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

Mar 28, 2024

The c.245T>G (p.V82G) alteration is located in exon 6 (coding exon 4) of the SNTG1 gene. This alteration results from a T to G substitution at nucleotide position 245, causing the valine (V) at amino acid position 82 to be replaced by a glycine (G). 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	0.98
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T;T;.;.;.;T;.;.;.;.;.;.
Eigen	Pathogenic	0.80
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.94	.;.;D;D;D;D;D;D;D;D;D;D
M_CAP	Benign	0.038	D
MetaRNN	Pathogenic	0.93	D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Uncertain	-0.24	T
MutationAssessor	Pathogenic	3.9	H;H;.;.;.;H;.;H;.;.;.;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.67	T
PROVEAN	Pathogenic	-6.2	D;.;.;.;.;D;.;D;.;D;.;.
REVEL	Uncertain	0.64
Sift	Pathogenic	0.0	D;.;.;.;.;D;.;D;.;D;.;.
Sift4G	Pathogenic	0.0010	D;.;.;.;.;D;.;D;.;D;.;.
Polyphen		0.98	D;D;.;.;.;D;.;D;.;.;.;.
Vest4		0.61
MutPred		0.81		Loss of stability (P = 0.024);Loss of stability (P = 0.024);.;Loss of stability (P = 0.024);.;Loss of stability (P = 0.024);Loss of stability (P = 0.024);Loss of stability (P = 0.024);Loss of stability (P = 0.024);Loss of stability (P = 0.024);Loss of stability (P = 0.024);Loss of stability (P = 0.024);
MVP		0.96
MPC		0.36
ClinPred		1.0	D
GERP RS		5.2
Varity_R		0.94
gMVP		0.80

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-51362253;