rs3011777

Variant names:

• chr10-50525751-A-G
• rs3011777
• NM_147156.4:c.-588-5830T>C

Variant summary

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

The NM_147156.4(SGMS1):​c.-588-5830T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 152,094 control chromosomes in the GnomAD database, including 12,877 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 0.38 (12877 hom., cov: 32)
• Consequence: SGMS1 NM_147156.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.707
• Publications: 5 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.501 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SGMS1	NM_147156.4	c.-588-5830T>C		intron_variant	Intron 2 of 10	ENST00000361781.7	NP_671512.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SGMS1	ENST00000361781.7	c.-588-5830T>C		intron_variant	Intron 2 of 10	1	NM_147156.4	ENSP00000354829.2

Frequencies

GnomAD3 genomes AF: 0.376 AC: 57127 AN: 151976 Hom.: 12873 Cov.: 32

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.474

Gnomad AMR AF: 0.395

Gnomad ASJ AF: 0.411

Gnomad EAS AF: 0.356

Gnomad SAS AF: 0.375

Gnomad FIN AF: 0.514

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.506

Gnomad OTH AF: 0.384

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

GnomAD4 genome AF: 0.376 AC: 57140 AN: 152094 Hom.: 12877 Cov.: 32 AF XY: 0.376 AC XY: 27929 AN XY: 74338

African (AFR) AF: 0.117 AC: 4876 AN: 41518

American (AMR) AF: 0.394 AC: 6027 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.411 AC: 1422 AN: 3464

East Asian (EAS) AF: 0.356 AC: 1841 AN: 5168

South Asian (SAS) AF: 0.376 AC: 1811 AN: 4822

European-Finnish (FIN) AF: 0.514 AC: 5433 AN: 10564

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.506 AC: 34386 AN: 67968

Other (OTH) AF: 0.384 AC: 811 AN: 2110

Alfa AF: 0.479 Hom.: 15735

Bravo AF: 0.358

Asia WGS AF: 0.359 AC: 1251 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.5
DANN	Benign	0.77
PhyloP100		0.71
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs3011777; hg19: chr10-52285511;