8-50248672-C-T

Variant names:

• chr8-50248672-C-T
• rs4873439
• NM_018967.5:c.-28+76037C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018967.5(SNTG1):​c.-28+76037C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 151,792 control chromosomes in the GnomAD database, including 5,304 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 0.26 (5304 hom., cov: 32)
• Consequence: SNTG1 NM_018967.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.391

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.356 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNTG1	NM_018967.5	c.-28+76037C>T		intron_variant	Intron 2 of 18	ENST00000642720.2	NP_061840.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNTG1	ENST00000642720.2	c.-28+76037C>T		intron_variant	Intron 2 of 18		NM_018967.5	ENSP00000493900.1

Frequencies

GnomAD3 genomes AF: 0.263 AC: 39857 AN: 151674 Hom.: 5302 Cov.: 32

Gnomad AFR AF: 0.242

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.244

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.370

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.257

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

GnomAD4 genome AF: 0.263 AC: 39892 AN: 151792 Hom.: 5304 Cov.: 32 AF XY: 0.263 AC XY: 19492 AN XY: 74152

Gnomad4 AFR AF: 0.242

Gnomad4 AMR AF: 0.266

Gnomad4 ASJ AF: 0.244

Gnomad4 EAS AF: 0.152

Gnomad4 SAS AF: 0.370

Gnomad4 FIN AF: 0.233

Gnomad4 NFE AF: 0.282

Gnomad4 OTH AF: 0.255

Alfa AF: 0.257 Hom.: 2466

Bravo AF: 0.263

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.1
DANN	Benign	0.73

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: rs4873439; hg19: chr8-51161232;