Variant 2-227991277-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001142644.2(SPHKAP):c.4771G>A(p.Glu1591Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0121 in 1,614,186 control chromosomes in the GnomAD database, including 137 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0093 ( 4 hom., cov: 33)

Exomes 𝑓: 0.012 ( 133 hom. )

Consequence

SPHKAP
NM_001142644.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.45

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:

SPHKAP (HGNC:):

SPHKAP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003917098).

BP6

Variant 2-227991277-C-T is Benign according to our data. Variant chr2-227991277-C-T is described in ClinVar as [Benign]. Clinvar id is 771702.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPHKAP	NM_001142644.2 linkuse as main transcript	c.4771G>A	p.Glu1591Lys	missense_variant	10/12	ENST00000392056.8	NP_001136116.1	Q2M3C7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SPHKAP	ENST00000392056.8 linkuse as main transcript	c.4771G>A	p.Glu1591Lys	missense_variant	10/12	1	NM_001142644.2	ENSP00000375909.3	Q2M3C7-1
SPHKAP	ENST00000344657.5 linkuse as main transcript	c.4684G>A	p.Glu1562Lys	missense_variant	9/11	1		ENSP00000339886.5	Q2M3C7-2
SPHKAP	ENST00000490603.1 linkuse as main transcript	n.264G>A		non_coding_transcript_exon_variant	3/4	4

Frequencies

GnomAD3 genomes

AF:

0.00932

AC:

1418

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00227

Gnomad AMI

AF:

0.0197

Gnomad AMR

AF:

0.0103

Gnomad ASJ

AF:

0.0150

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.0156

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0129

Gnomad OTH

AF:

0.0158

GnomAD3 exomes

AF:

0.00982

AC:

2467

AN:

251098

Hom.:

AF XY:

0.00999

AC XY:

1356

AN XY:

135690

show subpopulations

Gnomad AFR exome

AF:

0.00185

Gnomad AMR exome

AF:

0.00830

Gnomad ASJ exome

AF:

0.0102

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00235

Gnomad FIN exome

AF:

0.0136

Gnomad NFE exome

AF:

0.0139

Gnomad OTH exome

AF:

0.0162

GnomAD4 exome

AF:

0.0124

AC:

18101

AN:

1461846

Hom.:

133

Cov.:

AF XY:

0.0121

AC XY:

8827

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.00227

Gnomad4 AMR exome

AF:

0.00852

Gnomad4 ASJ exome

AF:

0.0117

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00310

Gnomad4 FIN exome

AF:

0.0145

Gnomad4 NFE exome

AF:

0.0140

Gnomad4 OTH exome

AF:

0.0113

GnomAD4 genome

AF:

0.00929

AC:

1416

AN:

152340

Hom.:

Cov.:

AF XY:

0.00930

AC XY:

693

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.00226

Gnomad4 AMR

AF:

0.0103

Gnomad4 ASJ

AF:

0.0150

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00290

Gnomad4 FIN

AF:

0.0156

Gnomad4 NFE

AF:

0.0129

Gnomad4 OTH

AF:

0.0156

Alfa

AF:

0.0126

Hom.:

Bravo

AF:

0.00884

TwinsUK

AF:

0.0165

AC:

ALSPAC

AF:

0.0148

AC:

ESP6500AA

AF:

0.00182

AC:

ESP6500EA

AF:

0.0141

AC:

121

ExAC

AF:

0.00955

AC:

1160

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.0154

EpiControl

AF:

0.0148

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.81

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.021

T;.

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.12

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.76

T;T

MetaRNN

Benign

0.0039

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.11

N;.

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.4

N;N

REVEL

Benign

0.045

Sift

Benign

0.42

T;T

Sift4G

Benign

0.53

T;T

Polyphen

0.011

B;B

Vest4

0.27

MVP

0.040

MPC

0.055

ClinPred

0.0092

GERP RS

4.3

Varity_R

0.059

gMVP

0.38

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over