chr19-48629377-G-C

Variant names:

• chr19-48629377-G-C
• rs3745733
• NM_020126.5:c.1569G>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_020126.5(SPHK2):​c.1569G>C​(p.Leu523Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,478 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SPHK2 NM_020126.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0850
• Publications: 0 publications found

Genes affected

SPHK2 (HGNC:18859): (sphingosine kinase 2) This gene encodes one of two sphingosine kinase isozymes that catalyze the phosphorylation of sphingosine into sphingosine 1-phosphate. Sphingosine 1-phosphate mediates many cellular processes including migration, proliferation and apoptosis, and also plays a role in several types of cancer by promoting angiogenesis and tumorigenesis. The encoded protein may play a role in breast cancer proliferation and chemoresistance. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Aug 2011]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP7: Synonymous conserved (PhyloP=0.085 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020126.5. 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
	SPHK2	NM_020126.5	MANE Select	c.1569G>C	p.Leu523Leu	synonymous	Exon 7 of 7	NP_064511.2
	SPHK2	NM_001204159.3		c.1569G>C	p.Leu523Leu	synonymous	Exon 7 of 7	NP_001191088.1	Q9NRA0-1
	SPHK2	NM_001204160.3		c.1461G>C	p.Leu487Leu	synonymous	Exon 6 of 6	NP_001191089.1	Q9NRA0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPHK2	ENST00000245222.9	TSL:1 MANE Select	c.1569G>C	p.Leu523Leu	synonymous	Exon 7 of 7	ENSP00000245222.3	Q9NRA0-1
	SPHK2	ENST00000599029.2	TSL:1	c.1461G>C	p.Leu487Leu	synonymous	Exon 5 of 6	ENSP00000472983.1	M0R344
	SPHK2	ENST00000598088.5	TSL:1	c.1569G>C	p.Leu523Leu	synonymous	Exon 7 of 7	ENSP00000469158.1	Q9NRA0-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1459478 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 726022

African (AFR) AF: 0.00 AC: 0 AN: 33468

American (AMR) AF: 0.00 AC: 0 AN: 44652

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26082

East Asian (EAS) AF: 0.00 AC: 0 AN: 39662

South Asian (SAS) AF: 0.00 AC: 0 AN: 86200

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51936

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111400

Other (OTH) AF: 0.00 AC: 0 AN: 60320

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	1.5
DANN	Benign	0.78
PhyloP100		0.085

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: rs3745733; hg19: chr19-49132634;