Genetic Variant SPHKAP:p.Ser1485Asn (chr2-227995689-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001142644.2(SPHKAP):c.4454G>A(p.Ser1485Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000015 in 1,595,592 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000097 ( 0 hom. )

Consequence

SPHKAP
NM_001142644.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.442

Publications

0 publications found

Variant links:

Genes affected

SPHKAP (HGNC:30619): (SPHK1 interactor, AKAP domain containing) Enables protein kinase A binding activity. Predicted to be located in Z disc. Predicted to be active in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

SPHKAP links:

LOC105373918 (HGNC:):

LOC105373918 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.053077966).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142644.2. 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
	SPHKAP	NM_001142644.2	MANE Select	c.4454G>A	p.Ser1485Asn	missense	Exon 8 of 12	NP_001136116.1	Q2M3C7-1
	SPHKAP	NM_030623.4		c.4454G>A	p.Ser1485Asn	missense	Exon 8 of 11	NP_085126.2	Q2M3C7-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SPHKAP	ENST00000392056.8	TSL:1 MANE Select	c.4454G>A	p.Ser1485Asn	missense	Exon 8 of 12	ENSP00000375909.3	Q2M3C7-1
SPHKAP	ENST00000344657.5	TSL:1	c.4454G>A	p.Ser1485Asn	missense	Exon 8 of 11	ENSP00000339886.5	Q2M3C7-2
SPHKAP	ENST00000490603.1	TSL:4	n.-54G>A		upstream_gene	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000658

AC:

AN:

151966

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000218

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000220

AC:

AN:

227620

AF XY:

0.0000163

show subpopulations

Gnomad AFR exome

AF:

0.000316

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000970

AC:

AN:

1443626

Hom.:

Cov.:

AF XY:

0.00000975

AC XY:

AN XY:

717594

show subpopulations

African (AFR)

AF:

0.000428

AC:

AN:

32708

American (AMR)

AF:

0.00

AC:

AN:

41586

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24750

East Asian (EAS)

AF:

0.00

AC:

AN:

39594

South Asian (SAS)

AF:

0.00

AC:

AN:

83552

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50160

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5576

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1106132

Other (OTH)

AF:

0.00

AC:

AN:

59568

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000658

AC:

AN:

151966

Hom.:

Cov.:

AF XY:

0.0000674

AC XY:

AN XY:

74220

show subpopulations

African (AFR)

AF:

0.000218

AC:

AN:

41370

American (AMR)

AF:

0.0000656

AC:

AN:

15248

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4808

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67980

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

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:

0.0000712

Hom.:

Bravo

AF:

0.0000907

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000247

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.82

CADD

Benign

8.4

(source)

DANN

Benign

0.78

DEOGEN2

Benign

0.024

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.99

FATHMM_MKL

Benign

0.075

LIST_S2

Benign

0.50

M_CAP

Benign

0.0050

MetaRNN

Benign

0.053

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.1

PhyloP100

0.44

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.1

REVEL

Benign

0.023

Sift

Benign

0.16

Sift4G

Uncertain

0.058

Polyphen

0.0010

Vest4

0.25

MVP

0.030

MPC

0.046

ClinPred

0.0073

GERP RS

0.63

Varity_R

0.058

gMVP

0.25

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