2-227981832-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001142644.2(SPHKAP):​c.4988G>A​(p.Arg1663Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000044 in 1,613,328 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.000079 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000040 ( 0 hom. )

Consequence

SPHKAP
NM_001142644.2 missense

Scores

1
18

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.578
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 Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.014619082).
BP6
Variant 2-227981832-C-T is Benign according to our data. Variant chr2-227981832-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3169070.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SPHKAPNM_001142644.2 linkc.4988G>A p.Arg1663Gln 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.4988G>A p.Arg1663Gln missense_variant Exon 12 of 12 1 NM_001142644.2 ENSP00000375909.3 Q2M3C7-1
SPHKAPENST00000344657.5 linkc.4901G>A p.Arg1634Gln missense_variant Exon 11 of 11 1 ENSP00000339886.5 Q2M3C7-2

Frequencies

GnomAD3 genomes
AF:
0.0000789
AC:
12
AN:
152070
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000217
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000294
Gnomad OTH
AF:
0.000479
GnomAD3 exomes
AF:
0.0000479
AC:
12
AN:
250274
Hom.:
0
AF XY:
0.0000517
AC XY:
7
AN XY:
135294
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.0000997
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000655
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000797
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000404
AC:
59
AN:
1461258
Hom.:
0
Cov.:
30
AF XY:
0.0000440
AC XY:
32
AN XY:
726962
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000696
Gnomad4 FIN exome
AF:
0.0000562
Gnomad4 NFE exome
AF:
0.0000396
Gnomad4 OTH exome
AF:
0.0000663
GnomAD4 genome
AF:
0.0000789
AC:
12
AN:
152070
Hom.:
0
Cov.:
33
AF XY:
0.0000673
AC XY:
5
AN XY:
74264
show subpopulations
Gnomad4 AFR
AF:
0.000217
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.000479
Alfa
AF:
0.0000444
Hom.:
0
Bravo
AF:
0.0000604
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000412
AC:
5

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Dec 01, 2022
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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
0.053
BayesDel_addAF
Benign
-0.53
T
BayesDel_noAF
Benign
-0.82
CADD
Benign
10
DANN
Benign
0.68
DEOGEN2
Benign
0.015
T;.
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.25
N
LIST_S2
Uncertain
0.88
D;D
M_CAP
Benign
0.0056
T
MetaRNN
Benign
0.015
T;T
MetaSVM
Benign
-0.94
T
MutationAssessor
Benign
-1.5
N;.
PrimateAI
Benign
0.24
T
PROVEAN
Benign
1.8
N;N
REVEL
Benign
0.036
Sift
Benign
1.0
T;T
Sift4G
Benign
1.0
T;T
Polyphen
0.010
B;B
Vest4
0.048
MVP
0.067
MPC
0.053
ClinPred
0.043
T
GERP RS
-1.2
Varity_R
0.042
gMVP
0.066

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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: rs147820842; hg19: chr2-228846548; COSMIC: COSV60876810; API