8-49955616-T-G

Variant names:

• chr8-49955616-T-G
• rs318885
• NM_018967.5:c.-103+43385T>G

Variant summary

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

The NM_018967.5(SNTG1):​c.-103+43385T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.868 in 152,244 control chromosomes in the GnomAD database, including 57,563 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 0.87 (57563 hom., cov: 33)
• Consequence: SNTG1 NM_018967.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.765
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNTG1	NM_018967.5	c.-103+43385T>G		intron_variant	Intron 1 of 18	ENST00000642720.2	NP_061840.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNTG1	ENST00000642720.2	c.-103+43385T>G		intron_variant	Intron 1 of 18		NM_018967.5	ENSP00000493900.1

Frequencies

GnomAD3 genomes AF: 0.868 AC: 132061 AN: 152126 Hom.: 57503 Cov.: 33

Gnomad AFR AF: 0.909

Gnomad AMI AF: 0.837

Gnomad AMR AF: 0.874

Gnomad ASJ AF: 0.788

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.929

Gnomad FIN AF: 0.883

Gnomad MID AF: 0.788

Gnomad NFE AF: 0.831

Gnomad OTH AF: 0.848

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

GnomAD4 genome AF: 0.868 AC: 132178 AN: 152244 Hom.: 57563 Cov.: 33 AF XY: 0.872 AC XY: 64926 AN XY: 74428

African (AFR) AF: 0.909 AC: 37765 AN: 41538

American (AMR) AF: 0.874 AC: 13369 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.788 AC: 2736 AN: 3470

East Asian (EAS) AF: 1.00 AC: 5186 AN: 5188

South Asian (SAS) AF: 0.928 AC: 4474 AN: 4820

European-Finnish (FIN) AF: 0.883 AC: 9349 AN: 10590

Middle Eastern (MID) AF: 0.796 AC: 234 AN: 294

European-Non Finnish (NFE) AF: 0.831 AC: 56508 AN: 68024

Other (OTH) AF: 0.849 AC: 1794 AN: 2112

Alfa AF: 0.861 Hom.: 9137

Bravo AF: 0.870

Asia WGS AF: 0.969 AC: 3368 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.4
DANN	Benign	0.71
PhyloP100		-0.77
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: rs318885; hg19: chr8-50868176;