10-50393354-A-G

Position:

• chr10-50393354-A-G

Variant summary

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

The NM_147156.4(SGMS1):​c.-232+40122T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 152,186 control chromosomes in the GnomAD database, including 2,554 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 0.16 (2554 hom., cov: 32)
• Consequence: SGMS1 NM_147156.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.557

Genes affected

SGMS1 (HGNC:29799): (sphingomyelin synthase 1) The protein encoded by this gene is predicted to be a five-pass transmembrane protein. This gene may be predominately expressed in brain. [provided by RefSeq, Jul 2008]

SGMS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SGMS1	NM_147156.4	c.-232+40122T>C		intron_variant		ENST00000361781.7	NP_671512.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SGMS1	ENST00000361781.7	c.-232+40122T>C		intron_variant		1	NM_147156.4	ENSP00000354829.2

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25116 AN: 152068 Hom.: 2559 Cov.: 32

Gnomad AFR AF: 0.0526

Gnomad AMI AF: 0.167

Gnomad AMR AF: 0.251

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.176

GnomAD3 exomes AF: 0.214 AC: 12 AN: 56 Hom.: 1 AF XY: 0.150 AC XY: 3 AN XY: 20

Gnomad AFR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.500

Gnomad NFE exome AF: 0.225

Gnomad OTH exome AF: 0.00

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

GnomAD4 genome AF: 0.165 AC: 25108 AN: 152186 Hom.: 2554 Cov.: 32 AF XY: 0.164 AC XY: 12191 AN XY: 74402

Gnomad4 AFR AF: 0.0524

Gnomad4 AMR AF: 0.251

Gnomad4 ASJ AF: 0.220

Gnomad4 EAS AF: 0.253

Gnomad4 SAS AF: 0.154

Gnomad4 FIN AF: 0.156

Gnomad4 NFE AF: 0.207

Gnomad4 OTH AF: 0.177

Alfa AF: 0.174 Hom.: 430

Bravo AF: 0.170

Asia WGS AF: 0.179 AC: 624 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.3
DANN	Benign	0.44

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: rs3739989; hg19: chr10-52153114;