10-50575886-G-C

Variant names:

• chr10-50575886-G-C
• rs7898315
• NM_147156.4:c.-589+14267C>G

Variant summary

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

The NM_147156.4(SGMS1):​c.-589+14267C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.456 in 151,710 control chromosomes in the GnomAD database, including 16,128 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 0.46 (16128 hom., cov: 31)
• Consequence: SGMS1 NM_147156.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.00
• Publications: 1 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]

SGMS1 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AR Classification: MODERATE Submitted by: PanelApp Australia

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.724 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_147156.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGMS1	NM_147156.4	MANE Select	c.-589+14267C>G		intron	N/A	NP_671512.1	Q86VZ5-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGMS1	ENST00000361781.7	TSL:1 MANE Select	c.-589+14267C>G		intron	N/A	ENSP00000354829.2	Q86VZ5-1
	SGMS1	ENST00000609445.6	TSL:4	c.-589+14267C>G		intron	N/A	ENSP00000521043.1
	SGMS1	ENST00000892763.1		c.-589+14267C>G		intron	N/A	ENSP00000562822.1

Frequencies

GnomAD3 genomes AF: 0.456 AC: 69120 AN: 151592 Hom.: 16108 Cov.: 31

Gnomad AFR AF: 0.512

Gnomad AMI AF: 0.374

Gnomad AMR AF: 0.473

Gnomad ASJ AF: 0.375

Gnomad EAS AF: 0.743

Gnomad SAS AF: 0.482

Gnomad FIN AF: 0.358

Gnomad MID AF: 0.455

Gnomad NFE AF: 0.415

Gnomad OTH AF: 0.448

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

GnomAD4 genome AF: 0.456 AC: 69183 AN: 151710 Hom.: 16128 Cov.: 31 AF XY: 0.456 AC XY: 33802 AN XY: 74172

African (AFR) AF: 0.512 AC: 21184 AN: 41386

American (AMR) AF: 0.473 AC: 7223 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.375 AC: 1300 AN: 3468

East Asian (EAS) AF: 0.743 AC: 3838 AN: 5164

South Asian (SAS) AF: 0.480 AC: 2311 AN: 4814

European-Finnish (FIN) AF: 0.358 AC: 3766 AN: 10508

Middle Eastern (MID) AF: 0.466 AC: 136 AN: 292

European-Non Finnish (NFE) AF: 0.415 AC: 28145 AN: 67790

Other (OTH) AF: 0.445 AC: 940 AN: 2110

Alfa AF: 0.414 Hom.: 1560

Bravo AF: 0.470

Asia WGS AF: 0.591 AC: 2054 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.61
DANN	Benign	0.77
PhyloP100		-2.0
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: rs7898315; hg19: chr10-52335646;