rs760448063

Variant names:

• chr14-63686470-C-G
• rs760448063
• NM_030791.4:c.961G>C

Your query was ambiguous. Multiple possible variants found:

• chr14-63686470-C-G
• chr14-63686470-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_030791.4(SGPP1):​c.961G>C​(p.Glu321Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,872 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E321K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SGPP1 NM_030791.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.89

Genes affected

SGPP1 (HGNC:17720): (sphingosine-1-phosphate phosphatase 1) Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid metabolite that regulates diverse biologic processes. SGPP1 catalyzes the degradation of S1P via salvage and recycling of sphingosine into long-chain ceramides (Mandala et al., 2000 [PubMed 10859351]; Le Stunff et al., 2007 [PubMed 17895250]).[supplied by OMIM, Jun 2009]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.066786826).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SGPP1	NM_030791.4	c.961G>C	p.Glu321Gln	missense_variant	Exon 3 of 3	ENST00000247225.7	NP_110418.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SGPP1	ENST00000247225.7	c.961G>C	p.Glu321Gln	missense_variant	Exon 3 of 3	1	NM_030791.4	ENSP00000247225.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251340 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135874

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461872 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727232

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	15
DANN	Benign	0.56
DEOGEN2	Benign	0.10	T
Eigen	Benign	-0.15
Eigen_PC	Benign	0.11
FATHMM_MKL	Benign	0.74	D
M_CAP	Benign	0.00056	T
MetaRNN	Benign	0.067	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.41	N
PrimateAI	Benign	0.48	T
PROVEAN	Benign	0.71	N
REVEL	Benign	0.069
Sift	Benign	0.48	T
Sift4G	Benign	0.52	T
Polyphen		0.024	B
Vest4		0.093
MutPred		0.31		Gain of catalytic residue at S325 (P = 0);
MVP		0.068
MPC		0.25
ClinPred		0.26	T
GERP RS		5.2
Varity_R		0.13
gMVP		0.56

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: rs760448063; hg19: chr14-64153188;