8-50384139-T-C

Variant names:

• chr8-50384139-T-C
• rs13278343
• NM_018967.5:c.-27-10073T>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.-27-10073T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.592 in 152,012 control chromosomes in the GnomAD database, including 26,857 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 0.59 (26857 hom., cov: 32)
• Consequence: SNTG1 NM_018967.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.543
• Publications: 1 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 = 0.799 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.-27-10073T>C		intron	N/A	NP_061840.1
	SNTG1	NM_001287813.3		c.-27-10073T>C		intron	N/A	NP_001274742.1
	SNTG1	NM_001321773.2		c.-27-10073T>C		intron	N/A	NP_001308702.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNTG1	ENST00000642720.2	MANE Select	c.-27-10073T>C		intron	N/A	ENSP00000493900.1
	SNTG1	ENST00000518864.5	TSL:1	c.-27-10073T>C		intron	N/A	ENSP00000429276.1
	SNTG1	ENST00000517473.5	TSL:1	c.-27-10073T>C		intron	N/A	ENSP00000431123.1

Frequencies

GnomAD3 genomes AF: 0.593 AC: 90022 AN: 151894 Hom.: 26855 Cov.: 32

Gnomad AFR AF: 0.586

Gnomad AMI AF: 0.705

Gnomad AMR AF: 0.623

Gnomad ASJ AF: 0.635

Gnomad EAS AF: 0.821

Gnomad SAS AF: 0.523

Gnomad FIN AF: 0.691

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.559

Gnomad OTH AF: 0.589

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

GnomAD4 genome AF: 0.592 AC: 90060 AN: 152012 Hom.: 26857 Cov.: 32 AF XY: 0.598 AC XY: 44403 AN XY: 74310

African (AFR) AF: 0.585 AC: 24276 AN: 41482

American (AMR) AF: 0.623 AC: 9518 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.635 AC: 2199 AN: 3462

East Asian (EAS) AF: 0.820 AC: 4223 AN: 5150

South Asian (SAS) AF: 0.523 AC: 2516 AN: 4812

European-Finnish (FIN) AF: 0.691 AC: 7308 AN: 10580

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.559 AC: 37981 AN: 67936

Other (OTH) AF: 0.592 AC: 1250 AN: 2112

Alfa AF: 0.573 Hom.: 3110

Bravo AF: 0.591

Asia WGS AF: 0.613 AC: 2132 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.4
DANN	Benign	0.85
PhyloP100		-0.54
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: rs13278343; hg19: chr8-51296699; COSMIC: COSV72839302; COSMIC: COSV72839302;