2-227981848-C-G
Variant names:
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
NM_001142644.2 missense
Scores
1
7
10
Clinical Significance
Conservation
PhyloP100: 3.58
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]
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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
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SPHKAP | ENST00000392056.8 | c.4972G>C | p.Val1658Leu | missense_variant | Exon 12 of 12 | 1 | NM_001142644.2 | ENSP00000375909.3 | ||
SPHKAP | ENST00000344657.5 | c.4885G>C | p.Val1629Leu | missense_variant | Exon 11 of 11 | 1 | ENSP00000339886.5 |
Frequencies
GnomAD3 genomes AF: 0.00657 AC: 999AN: 152146Hom.: 4 Cov.: 33
GnomAD3 genomes
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33
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GnomAD3 exomes AF: 0.00811 AC: 2023AN: 249464Hom.: 10 AF XY: 0.00787 AC XY: 1062AN XY: 134872
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GnomAD4 exome AF: 0.00875 AC: 12777AN: 1460698Hom.: 60 Cov.: 30 AF XY: 0.00863 AC XY: 6268AN XY: 726646
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GnomAD4 genome AF: 0.00655 AC: 998AN: 152264Hom.: 4 Cov.: 33 AF XY: 0.00681 AC XY: 507AN XY: 74436
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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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
D;B
Vest4
MutPred
Loss of MoRF binding (P = 0.0972);.;
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at