chr8-50658612-G-A

Variant names:

• chr8-50658612-G-A
• rs1911830
• NM_018967.5:c.987G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_018967.5(SNTG1):​c.987G>A​(p.Thr329Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.648 in 1,603,866 control chromosomes in the GnomAD database, including 345,076 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.56 (25751 hom., cov: 32)
  • Exomes 𝑓: 0.66 (319325 hom.)
• Consequence: SNTG1 NM_018967.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0870
• Publications: 16 publications found

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

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP7: Synonymous conserved (PhyloP=0.087 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.672 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018967.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNTG1	NM_018967.5	MANE Select	c.987G>A	p.Thr329Thr	synonymous	Exon 15 of 19	NP_061840.1
	SNTG1	NM_001287813.3		c.987G>A	p.Thr329Thr	synonymous	Exon 16 of 20	NP_001274742.1
	SNTG1	NM_001321773.2		c.987G>A	p.Thr329Thr	synonymous	Exon 14 of 18	NP_001308702.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNTG1	ENST00000642720.2	MANE Select	c.987G>A	p.Thr329Thr	synonymous	Exon 15 of 19	ENSP00000493900.1
	SNTG1	ENST00000518864.5	TSL:1	c.987G>A	p.Thr329Thr	synonymous	Exon 16 of 20	ENSP00000429276.1
	SNTG1	ENST00000517473.5	TSL:1	c.987G>A	p.Thr329Thr	synonymous	Exon 14 of 17	ENSP00000431123.1

Frequencies

GnomAD3 genomes AF: 0.556 AC: 84548 AN: 151934 Hom.: 25755 Cov.: 32

Gnomad AFR AF: 0.288

Gnomad AMI AF: 0.680

Gnomad AMR AF: 0.592

Gnomad ASJ AF: 0.647

Gnomad EAS AF: 0.665

Gnomad SAS AF: 0.469

Gnomad FIN AF: 0.720

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.677

Gnomad OTH AF: 0.570

GnomAD2 exomes AF: 0.612 AC: 151532 AN: 247602 AF XY: 0.616

Gnomad AFR exome AF: 0.281

Gnomad AMR exome AF: 0.558

Gnomad ASJ exome AF: 0.645

Gnomad EAS exome AF: 0.657

Gnomad FIN exome AF: 0.713

Gnomad NFE exome AF: 0.682

Gnomad OTH exome AF: 0.634

GnomAD4 exome AF: 0.658 AC: 954660 AN: 1451814 Hom.: 319325 Cov.: 31 AF XY: 0.654 AC XY: 472476 AN XY: 722636

African (AFR) AF: 0.274 AC: 9092 AN: 33186

American (AMR) AF: 0.564 AC: 24870 AN: 44094

Ashkenazi Jewish (ASJ) AF: 0.645 AC: 16738 AN: 25940

East Asian (EAS) AF: 0.669 AC: 26326 AN: 39334

South Asian (SAS) AF: 0.480 AC: 41031 AN: 85558

European-Finnish (FIN) AF: 0.710 AC: 37846 AN: 53270

Middle Eastern (MID) AF: 0.600 AC: 3444 AN: 5742

European-Non Finnish (NFE) AF: 0.686 AC: 757526 AN: 1104692

Other (OTH) AF: 0.630 AC: 37787 AN: 59998

GnomAD4 genome AF: 0.556 AC: 84538 AN: 152052 Hom.: 25751 Cov.: 32 AF XY: 0.558 AC XY: 41439 AN XY: 74316

African (AFR) AF: 0.288 AC: 11937 AN: 41454

American (AMR) AF: 0.591 AC: 9017 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.647 AC: 2244 AN: 3470

East Asian (EAS) AF: 0.664 AC: 3433 AN: 5168

South Asian (SAS) AF: 0.468 AC: 2256 AN: 4820

European-Finnish (FIN) AF: 0.720 AC: 7619 AN: 10582

Middle Eastern (MID) AF: 0.571 AC: 168 AN: 294

European-Non Finnish (NFE) AF: 0.677 AC: 46050 AN: 67976

Other (OTH) AF: 0.566 AC: 1194 AN: 2110

Alfa AF: 0.616 Hom.: 24906

Bravo AF: 0.536

Asia WGS AF: 0.514 AC: 1785 AN: 3476

EpiCase AF: 0.671

EpiControl AF: 0.673

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	5.0
DANN	Benign	0.67
PhyloP100		0.087
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
Splicevardb		1.0
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

Other links and lift over

dbSNP: rs1911830; hg19: chr8-51571172; COSMIC: COSV52471518;