rs12356013

Variant names:

• chr10-50361470-G-A
• rs12356013
• NM_147156.4:c.-231-17125C>T

Variant summary

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

The NM_147156.4(SGMS1):​c.-231-17125C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0505 in 152,216 control chromosomes in the GnomAD database, including 285 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 0.050 (285 hom., cov: 32)
• Consequence: SGMS1 NM_147156.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0150
• Publications: 3 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0681 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SGMS1	NM_147156.4	c.-231-17125C>T		intron_variant	Intron 6 of 10	ENST00000361781.7	NP_671512.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SGMS1	ENST00000361781.7	c.-231-17125C>T		intron_variant	Intron 6 of 10	1	NM_147156.4	ENSP00000354829.2

Frequencies

GnomAD3 genomes AF: 0.0505 AC: 7684 AN: 152098 Hom.: 285 Cov.: 32

Gnomad AFR AF: 0.0125

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.0551

Gnomad ASJ AF: 0.0931

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0344

Gnomad FIN AF: 0.0768

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0697

Gnomad OTH AF: 0.0683

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

GnomAD4 genome AF: 0.0505 AC: 7683 AN: 152216 Hom.: 285 Cov.: 32 AF XY: 0.0501 AC XY: 3726 AN XY: 74410

African (AFR) AF: 0.0125 AC: 519 AN: 41540

American (AMR) AF: 0.0549 AC: 840 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0931 AC: 323 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.0349 AC: 168 AN: 4818

European-Finnish (FIN) AF: 0.0768 AC: 813 AN: 10588

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0697 AC: 4743 AN: 68016

Other (OTH) AF: 0.0676 AC: 143 AN: 2116

Alfa AF: 0.0442 Hom.: 95

Bravo AF: 0.0468

Asia WGS AF: 0.0120 AC: 40 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.3
DANN	Benign	0.44
PhyloP100		-0.015
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: rs12356013; hg19: chr10-52121230;