8-50632033-T-C

Variant names:

• chr8-50632033-T-C
• rs1384830
• NM_018967.5:c.850-24876T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018967.5(SNTG1):​c.850-24876T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 152,100 control chromosomes in the GnomAD database, including 8,704 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 0.23 (8704 hom., cov: 33)
• Consequence: SNTG1 NM_018967.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.436
• Publications: 3 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.617 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNTG1	NM_018967.5	c.850-24876T>C		intron_variant	Intron 13 of 18	ENST00000642720.2	NP_061840.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNTG1	ENST00000642720.2	c.850-24876T>C		intron_variant	Intron 13 of 18		NM_018967.5	ENSP00000493900.1

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34248 AN: 151982 Hom.: 8666 Cov.: 33

Gnomad AFR AF: 0.623

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.0727

Gnomad EAS AF: 0.132

Gnomad SAS AF: 0.187

Gnomad FIN AF: 0.0569

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.0441

Gnomad OTH AF: 0.187

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.226 AC: 34351 AN: 152100 Hom.: 8704 Cov.: 33 AF XY: 0.224 AC XY: 16674 AN XY: 74350

African (AFR) AF: 0.623 AC: 25822 AN: 41434

American (AMR) AF: 0.173 AC: 2646 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0727 AC: 252 AN: 3468

East Asian (EAS) AF: 0.133 AC: 685 AN: 5164

South Asian (SAS) AF: 0.186 AC: 898 AN: 4826

European-Finnish (FIN) AF: 0.0569 AC: 603 AN: 10598

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.0441 AC: 2999 AN: 68018

Other (OTH) AF: 0.189 AC: 399 AN: 2110

Alfa AF: 0.167 Hom.: 1916

Bravo AF: 0.248

Asia WGS AF: 0.195 AC: 679 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.73
DANN	Benign	0.40
PhyloP100		-0.44
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1384830; hg19: chr8-51544593;