chr14-63727580-C-T

Position:

• chr14-63727580-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_030791.4(SGPP1):​c.365G>A​(p.Arg122His) variant causes a missense 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SGPP1 NM_030791.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.187

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=0.07981017).
• BP6: Variant 14-63727580-C-T is Benign according to our data. Variant chr14-63727580-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2534541.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SGPP1	NM_030791.4	c.365G>A	p.Arg122His	missense_variant	1/3	ENST00000247225.7	NP_110418.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SGPP1	ENST00000247225.7	c.365G>A	p.Arg122His	missense_variant	1/3	1	NM_030791.4	ENSP00000247225.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 07, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	12
DANN	Benign	0.96
DEOGEN2	Benign	0.13	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.072	N
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.080	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.035	N
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.84	N
REVEL	Benign	0.011
Sift	Benign	0.23	T
Sift4G	Benign	0.56	T
Polyphen		0.0	B
Vest4		0.055
MutPred		0.39		Gain of catalytic residue at N125 (P = 0);
MVP		0.10
MPC		1.3
ClinPred		0.10	T
GERP RS		-3.3
Varity_R		0.035
gMVP		0.27

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-64194298;