rs201987985

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_182965.3(SPHK1):c.95C>A(p.Ala32Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00213 in 1,560,368 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A32V) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0022 ( 4 hom. )

Consequence

SPHK1
NM_182965.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.67

Publications

4 publications found

Variant links:

Genes affected

SPHK1 (HGNC:11240): (sphingosine kinase 1) The protein encoded by this gene catalyzes the phosphorylation of sphingosine to form sphingosine-1-phosphate (S1P), a lipid mediator with both intra- and extracellular functions. Intracellularly, S1P regulates proliferation and survival, and extracellularly, it is a ligand for cell surface G protein-coupled receptors. This protein, and its product S1P, play a key role in TNF-alpha signaling and the NF-kappa-B activation pathway important in inflammatory, antiapoptotic, and immune processes. Phosphorylation of this protein alters its catalytic activity and promotes its translocation to the plasma membrane. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Sep 2017]

SPHK1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0059254467).

BP6

Variant 17-76385481-C-A is Benign according to our data. Variant chr17-76385481-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 731910.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 185 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182965.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SPHK1	NM_001142601.2	MANE Select	c.-164C>A		5_prime_UTR	Exon 2 of 6	NP_001136073.1	Q9NYA1-1
SPHK1	NM_182965.3		c.95C>A	p.Ala32Asp	missense	Exon 2 of 6	NP_892010.2	Q9NYA1-2
SPHK1	NM_021972.4		c.-164C>A		5_prime_UTR	Exon 2 of 6	NP_068807.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SPHK1	ENST00000323374.8	TSL:1	c.95C>A	p.Ala32Asp	missense	Exon 2 of 6	ENSP00000313681.3	Q9NYA1-2
SPHK1	ENST00000592299.6	TSL:1 MANE Select	c.-164C>A		5_prime_UTR	Exon 2 of 6	ENSP00000465726.2	Q9NYA1-1
SPHK1	ENST00000590959.5	TSL:1	c.-164C>A		5_prime_UTR	Exon 2 of 6	ENSP00000468547.1	Q9NYA1-3

Frequencies

GnomAD3 genomes

AF:

0.00122

AC:

185

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000579

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000523

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.000282

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00215

Gnomad OTH

AF:

0.000958

GnomAD2 exomes

AF:

0.00112

AC:

189

AN:

168766

AF XY:

0.00114

show subpopulations

Gnomad AFR exome

AF:

0.000338

Gnomad AMR exome

AF:

0.000380

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000411

Gnomad NFE exome

AF:

0.00215

Gnomad OTH exome

AF:

0.00130

GnomAD4 exome

AF:

0.00223

AC:

3134

AN:

1408032

Hom.:

Cov.:

AF XY:

0.00218

AC XY:

1521

AN XY:

697360

show subpopulations

African (AFR)

AF:

0.000463

AC:

AN:

32394

American (AMR)

AF:

0.000548

AC:

AN:

40118

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25396

East Asian (EAS)

AF:

0.00

AC:

AN:

37582

South Asian (SAS)

AF:

0.000369

AC:

AN:

81404

European-Finnish (FIN)

AF:

0.000310

AC:

AN:

35464

Middle Eastern (MID)

AF:

0.000975

AC:

AN:

4104

European-Non Finnish (NFE)

AF:

0.00271

AC:

2961

AN:

1093032

Other (OTH)

AF:

0.00155

AC:

AN:

58538

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

182

365

547

730

912

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

116

232

348

464

580

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00121

AC:

185

AN:

152336

Hom.:

Cov.:

AF XY:

0.00110

AC XY:

AN XY:

74496

show subpopulations

African (AFR)

AF:

0.000577

AC:

AN:

41586

American (AMR)

AF:

0.000523

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.000414

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.000282

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00215

AC:

146

AN:

68026

Other (OTH)

AF:

0.000948

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000967

Hom.:

Bravo

AF:

0.00126

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00168

AC:

ExAC

AF:

0.00111

AC:

126

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.78

CADD

Benign

5.4

(source)

DANN

Benign

0.93

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.37

M_CAP

Benign

0.022

MetaRNN

Benign

0.0059

MetaSVM

Benign

-1.0

PhyloP100

-2.7

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-0.82

REVEL

Benign

0.014

Sift

Benign

0.099

Sift4G

Benign

0.16

Polyphen

0.0030

Vest4

0.13

MVP

0.10

MPC

0.46

ClinPred

0.0027

GERP RS

-2.6

PromoterAI

0.052

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=96/4

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over