8-50536768-T-G

Variant summary

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

The NM_018967.5(SNTG1):c.640T>G(p.Ser214Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,684 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. S214S) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: SNTG1 NM_018967.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.98

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=0.092362374).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNTG1	NM_018967.5	c.640T>G	p.Ser214Ala	missense_variant	11/19	ENST00000642720.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNTG1	ENST00000642720.2	c.640T>G	p.Ser214Ala	missense_variant	11/19		NM_018967.5	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000399 AC: 1 AN: 250874 Hom.: 0 AF XY: 0.00000738 AC XY: 1 AN XY: 135548

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000883

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461684 Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4 AN XY: 727138

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.: 33

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

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

Jan 30, 2024

The c.640T>G (p.S214A) alteration is located in exon 11 (coding exon 9) of the SNTG1 gene. This alteration results from a T to G substitution at nucleotide position 640, causing the serine (S) at amino acid position 214 to be replaced by an alanine (A). 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	0.069
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
Cadd	Benign	8.4
Dann	Benign	0.24
DEOGEN2	Benign	0.022	T;T;.;.;T;.;.;.;.;.;.
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.78
FATHMM_MKL	Uncertain	0.87	D
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.092	T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.74	N;N;.;.;N;.;.;N;.;.;.
MutationTaster	Benign	0.99	D;D;D;D
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	1.8	N;.;.;.;N;.;.;N;.;.;.
REVEL	Benign	0.29
Sift	Benign	1.0	T;.;.;.;T;.;.;T;.;.;.
Sift4G	Benign	1.0	T;.;.;.;T;.;.;T;.;.;.
Polyphen		0.0	B;B;.;.;B;.;.;B;.;.;.
Vest4		0.41
MutPred		0.40		Loss of disorder (P = 0.1015);Loss of disorder (P = 0.1015);.;.;Loss of disorder (P = 0.1015);Loss of disorder (P = 0.1015);.;Loss of disorder (P = 0.1015);Loss of disorder (P = 0.1015);Loss of disorder (P = 0.1015);Loss of disorder (P = 0.1015);
MVP		0.65
MPC		0.047
ClinPred		0.018	T
GERP RS		3.7
Varity_R		0.12
gMVP		0.51

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: rs779537168; hg19: chr8-51449328;