NM_001375905.1:c.148C>A

Variant names:

• chr4-107895701-C-A
• rs1560667389
• NM_001375905.1:c.148C>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001375905.1(SGMS2):​c.148C>A​(p.Arg50Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: SGMS2 NM_001375905.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.69
• Publications: 0 publications found

Genes affected

SGMS2 (HGNC:28395): (sphingomyelin synthase 2) Sphingomyelin, a major component of cell and Golgi membranes, is made by the transfer of phosphocholine from phosphatidylcholine onto ceramide, with diacylglycerol as a side product. The protein encoded by this gene is an enzyme that catalyzes this reaction primarily at the cell membrane. The synthesis is reversible, and this enzyme can catalyze the reaction in either direction. The encoded protein is required for cell growth. Three transcript variants encoding the same protein have been found for this gene. There is evidence for more variants, but the full-length nature of their transcripts has not been determined.[provided by RefSeq, Oct 2008]

CYP2U1-AS1 (HGNC:54817): (CYP2U1 and SGMS2 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP7: Synonymous conserved (PhyloP=2.69 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001375905.1. 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
	SGMS2	NM_001375905.1	MANE Select	c.148C>A	p.Arg50Arg	synonymous	Exon 3 of 7	NP_001362834.1	Q8NHU3
	SGMS2	NM_001136257.2		c.148C>A	p.Arg50Arg	synonymous	Exon 2 of 6	NP_001129729.1	Q8NHU3
	SGMS2	NM_001136258.2		c.148C>A	p.Arg50Arg	synonymous	Exon 3 of 7	NP_001129730.1	Q8NHU3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGMS2	ENST00000690982.1	MANE Select	c.148C>A	p.Arg50Arg	synonymous	Exon 3 of 7	ENSP00000508566.1	Q8NHU3
	SGMS2	ENST00000359079.8	TSL:1	c.148C>A	p.Arg50Arg	synonymous	Exon 2 of 6	ENSP00000351981.4	Q8NHU3
	SGMS2	ENST00000394684.8	TSL:1	c.148C>A	p.Arg50Arg	synonymous	Exon 3 of 7	ENSP00000378176.4	Q8NHU3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	14
DANN	Benign	0.71
PhyloP100		2.7

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: rs1560667389; hg19: chr4-108816857;