10-50447664-C-T

Variant summary

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

The NM_147156.4(SGMS1):c.-313+13009G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.857 in 152,238 control chromosomes in the GnomAD database, including 56,158 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 0.86 (56158 hom., cov: 33)
• Consequence: SGMS1 NM_147156.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.155

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.973 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SGMS1	NM_147156.4	c.-313+13009G>A		intron_variant		ENST00000361781.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SGMS1	ENST00000361781.7	c.-313+13009G>A		intron_variant		1	NM_147156.4	P1
SGMS1	ENST00000429490.5	c.-313+13009G>A		intron_variant		5
SGMS1	ENST00000619438.4	c.-313+13009G>A		intron_variant		5
SGMS1	ENST00000609445.5	n.438+13009G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.857 AC: 130369 AN: 152120 Hom.: 56104 Cov.: 33

Gnomad AFR AF: 0.921

Gnomad AMI AF: 0.851

Gnomad AMR AF: 0.879

Gnomad ASJ AF: 0.795

Gnomad EAS AF: 0.996

Gnomad SAS AF: 0.797

Gnomad FIN AF: 0.792

Gnomad MID AF: 0.819

Gnomad NFE AF: 0.820

Gnomad OTH AF: 0.857

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

GnomAD4 genome AF: 0.857 AC: 130483 AN: 152238 Hom.: 56158 Cov.: 33 AF XY: 0.856 AC XY: 63713 AN XY: 74424

Gnomad4 AFR AF: 0.921

Gnomad4 AMR AF: 0.878

Gnomad4 ASJ AF: 0.795

Gnomad4 EAS AF: 0.996

Gnomad4 SAS AF: 0.797

Gnomad4 FIN AF: 0.792

Gnomad4 NFE AF: 0.820

Gnomad4 OTH AF: 0.857

Alfa AF: 0.765 Hom.: 2237

Bravo AF: 0.869

Asia WGS AF: 0.895 AC: 3104 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	1.8
Dann	Benign	0.50

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: rs1211373; hg19: chr10-52207424;