chr1-204228972-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_014935.5(PLEKHA6):ā€‹c.2716G>Cā€‹(p.Glu906Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000384 in 1,614,054 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000026 ( 0 hom., cov: 32)
Exomes š‘“: 0.000040 ( 0 hom. )

Consequence

PLEKHA6
NM_014935.5 missense

Scores

3
4
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.95
Variant links:
Genes affected
PLEKHA6 (HGNC:17053): (pleckstrin homology domain containing A6)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.3343991).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PLEKHA6NM_014935.5 linkuse as main transcriptc.2716G>C p.Glu906Gln missense_variant 19/23 ENST00000272203.8 NP_055750.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PLEKHA6ENST00000272203.8 linkuse as main transcriptc.2716G>C p.Glu906Gln missense_variant 19/231 NM_014935.5 ENSP00000272203 P2
PLEKHA6ENST00000637508.1 linkuse as main transcriptc.3088G>C p.Glu1030Gln missense_variant 23/275 ENSP00000490182 A2
PLEKHA6ENST00000414478.1 linkuse as main transcriptc.2776G>C p.Glu926Gln missense_variant 19/235 ENSP00000402046

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152168
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000942
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000557
AC:
14
AN:
251478
Hom.:
0
AF XY:
0.0000883
AC XY:
12
AN XY:
135914
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000653
Gnomad FIN exome
AF:
0.0000462
Gnomad NFE exome
AF:
0.0000967
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000397
AC:
58
AN:
1461886
Hom.:
0
Cov.:
33
AF XY:
0.0000371
AC XY:
27
AN XY:
727246
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.0000374
Gnomad4 NFE exome
AF:
0.0000450
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152168
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74324
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000942
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000564
Hom.:
0
Bravo
AF:
0.00000756
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000576
AC:
7
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

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 GeneticsNov 08, 2021The c.2716G>C (p.E906Q) alteration is located in exon 19 (coding exon 17) of the PLEKHA6 gene. This alteration results from a G to C substitution at nucleotide position 2716, causing the glutamic acid (E) at amino acid position 906 to be replaced by a glutamine (Q). 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
Benign
0.28
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.22
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.089
T;T;.
Eigen
Pathogenic
0.76
Eigen_PC
Pathogenic
0.73
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.95
D;D;D
M_CAP
Benign
0.020
T
MetaRNN
Benign
0.33
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.6
M;.;.
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.68
T
PROVEAN
Benign
-2.3
N;.;N
REVEL
Benign
0.18
Sift
Benign
0.072
T;.;T
Sift4G
Benign
0.16
T;.;T
Polyphen
0.99
D;.;.
Vest4
0.85
MVP
0.24
MPC
0.34
ClinPred
0.41
T
GERP RS
5.4
Varity_R
0.30
gMVP
0.64

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: rs145574759; hg19: chr1-204198100; API