2-227981848-C-G

Variant summary

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

The NM_001142644.2(SPHKAP):​c.4972G>C​(p.Val1658Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00854 in 1,612,962 control chromosomes in the GnomAD database, including 64 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0066 ( 4 hom., cov: 33)
Exomes 𝑓: 0.0087 ( 60 hom. )

Consequence

SPHKAP
NM_001142644.2 missense

Scores

1
7
10

Clinical Significance

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

Conservation

PhyloP100: 3.58
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]

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=0.0047121346).
BP6
Variant 2-227981848-C-G is Benign according to our data. Variant chr2-227981848-C-G is described in ClinVar as [Benign]. Clinvar id is 788963.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 rank MANE Protein UniProt
SPHKAPNM_001142644.2 linkc.4972G>C p.Val1658Leu missense_variant Exon 12 of 12 ENST00000392056.8 NP_001136116.1 Q2M3C7-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SPHKAPENST00000392056.8 linkc.4972G>C p.Val1658Leu missense_variant Exon 12 of 12 1 NM_001142644.2 ENSP00000375909.3 Q2M3C7-1
SPHKAPENST00000344657.5 linkc.4885G>C p.Val1629Leu missense_variant Exon 11 of 11 1 ENSP00000339886.5 Q2M3C7-2

Frequencies

GnomAD3 genomes
AF:
0.00657
AC:
999
AN:
152146
Hom.:
4
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00164
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00805
Gnomad ASJ
AF:
0.00288
Gnomad EAS
AF:
0.00982
Gnomad SAS
AF:
0.00477
Gnomad FIN
AF:
0.00198
Gnomad MID
AF:
0.0222
Gnomad NFE
AF:
0.00989
Gnomad OTH
AF:
0.0110
GnomAD3 exomes
AF:
0.00811
AC:
2023
AN:
249464
Hom.:
10
AF XY:
0.00787
AC XY:
1062
AN XY:
134872
show subpopulations
Gnomad AFR exome
AF:
0.00173
Gnomad AMR exome
AF:
0.0118
Gnomad ASJ exome
AF:
0.00440
Gnomad EAS exome
AF:
0.00848
Gnomad SAS exome
AF:
0.00562
Gnomad FIN exome
AF:
0.00200
Gnomad NFE exome
AF:
0.0101
Gnomad OTH exome
AF:
0.00626
GnomAD4 exome
AF:
0.00875
AC:
12777
AN:
1460698
Hom.:
60
Cov.:
30
AF XY:
0.00863
AC XY:
6268
AN XY:
726646
show subpopulations
Gnomad4 AFR exome
AF:
0.00186
Gnomad4 AMR exome
AF:
0.0109
Gnomad4 ASJ exome
AF:
0.00414
Gnomad4 EAS exome
AF:
0.00976
Gnomad4 SAS exome
AF:
0.00526
Gnomad4 FIN exome
AF:
0.00242
Gnomad4 NFE exome
AF:
0.00959
Gnomad4 OTH exome
AF:
0.00726
GnomAD4 genome
AF:
0.00655
AC:
998
AN:
152264
Hom.:
4
Cov.:
33
AF XY:
0.00681
AC XY:
507
AN XY:
74436
show subpopulations
Gnomad4 AFR
AF:
0.00164
Gnomad4 AMR
AF:
0.00804
Gnomad4 ASJ
AF:
0.00288
Gnomad4 EAS
AF:
0.00984
Gnomad4 SAS
AF:
0.00477
Gnomad4 FIN
AF:
0.00198
Gnomad4 NFE
AF:
0.00990
Gnomad4 OTH
AF:
0.0109
Alfa
AF:
0.00375
Hom.:
0
Bravo
AF:
0.00720
TwinsUK
AF:
0.0102
AC:
38
ALSPAC
AF:
0.00856
AC:
33
ESP6500AA
AF:
0.00182
AC:
8
ESP6500EA
AF:
0.00930
AC:
80
ExAC
AF:
0.00793
AC:
963
Asia WGS
AF:
0.00693
AC:
24
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Jan 24, 2018
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.68
BayesDel_addAF
Benign
-0.39
T
BayesDel_noAF
Benign
-0.32
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.048
T;.
Eigen
Uncertain
0.45
Eigen_PC
Uncertain
0.52
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Uncertain
0.86
D;D
MetaRNN
Benign
0.0047
T;T
MetaSVM
Benign
-1.2
T
MutationAssessor
Uncertain
2.2
M;.
PrimateAI
Uncertain
0.54
T
PROVEAN
Benign
-0.82
N;N
REVEL
Benign
0.081
Sift
Benign
0.14
T;T
Sift4G
Benign
0.29
T;T
Polyphen
1.0
D;B
Vest4
0.45
MutPred
0.39
Loss of MoRF binding (P = 0.0972);.;
MVP
0.14
MPC
0.12
ClinPred
0.020
T
GERP RS
5.8
Varity_R
0.27
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

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

Other links and lift over

dbSNP: rs61755300; hg19: chr2-228846564; COSMIC: COSV60877730; API