1-204228762-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014935.5(PLEKHA6):​c.2851G>T​(p.Val951Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

PLEKHA6
NM_014935.5 missense

Scores

1
6
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.41
Variant links:
Genes affected
PLEKHA6 (HGNC:17053): (pleckstrin homology domain containing A6)

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.22607991).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PLEKHA6NM_014935.5 linkuse as main transcriptc.2851G>T p.Val951Leu missense_variant 20/23 ENST00000272203.8 NP_055750.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PLEKHA6ENST00000272203.8 linkuse as main transcriptc.2851G>T p.Val951Leu missense_variant 20/231 NM_014935.5 ENSP00000272203 P2
PLEKHA6ENST00000637508.1 linkuse as main transcriptc.3223G>T p.Val1075Leu missense_variant 24/275 ENSP00000490182 A2
PLEKHA6ENST00000414478.1 linkuse as main transcriptc.2911G>T p.Val971Leu missense_variant 20/235 ENSP00000402046

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMay 24, 2024The c.2851G>T (p.V951L) alteration is located in exon 20 (coding exon 18) of the PLEKHA6 gene. This alteration results from a G to T substitution at nucleotide position 2851, causing the valine (V) at amino acid position 951 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.69
BayesDel_addAF
Benign
-0.20
T
BayesDel_noAF
Benign
-0.43
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.065
T;T;.
Eigen
Uncertain
0.55
Eigen_PC
Uncertain
0.55
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Uncertain
0.93
D;D;D
M_CAP
Benign
0.014
T
MetaRNN
Benign
0.23
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.93
L;.;.
MutationTaster
Benign
0.97
D;D
PrimateAI
Uncertain
0.69
T
PROVEAN
Benign
-1.3
N;.;N
REVEL
Benign
0.14
Sift
Benign
0.21
T;.;T
Sift4G
Benign
0.15
T;.;T
Polyphen
0.93
P;.;.
Vest4
0.19
MutPred
0.15
Loss of methylation at K950 (P = 0.0359);.;.;
MVP
0.10
MPC
0.12
ClinPred
0.49
T
GERP RS
5.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.20
gMVP
0.53

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: rs1201343517; hg19: chr1-204197890; API