15-40281610-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001190479.3(ANKRD63):​c.977G>A​(p.Gly326Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000582 in 1,528,504 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 34)
Exomes 𝑓: 0.000057 ( 0 hom. )

Consequence

ANKRD63
NM_001190479.3 missense

Scores

1
5
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0630
Variant links:
Genes affected
ANKRD63 (HGNC:40027): (ankyrin repeat domain 63)
PLCB2 (HGNC:9055): (phospholipase C beta 2) The protein encoded by this gene is a phosphodiesterase that catalyzes the hydrolysis of phosphatidylinositol 4,5-bisphosphate to the second messengers inositol 1,4,5-trisphosphate (IP3) and diacylglycerol. The encoded protein is activated by G proteins and has been shown to be involved in the type 2 taste receptor signal transduction pathway. In addition, nuclear factor kappa B can regulate the transcription of this gene, whose protein product is also an important regulator of platelet responses. [provided by RefSeq, Jan 2017]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.027334452).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ANKRD63NM_001190479.3 linkc.977G>A p.Gly326Asp missense_variant Exon 1 of 1 ENST00000434396.2 NP_001177408.1 C9JTQ0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ANKRD63ENST00000434396.2 linkc.977G>A p.Gly326Asp missense_variant Exon 1 of 1 6 NM_001190479.3 ENSP00000399547.1 C9JTQ0
PLCB2ENST00000560009.1 linkn.394+2829G>A intron_variant Intron 2 of 2 4

Frequencies

GnomAD3 genomes
AF:
0.0000723
AC:
11
AN:
152208
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00259
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:
0.00
GnomAD3 exomes
AF:
0.000130
AC:
16
AN:
123494
Hom.:
0
AF XY:
0.000133
AC XY:
9
AN XY:
67810
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000430
Gnomad ASJ exome
AF:
0.00154
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000436
Gnomad OTH exome
AF:
0.000261
GnomAD4 exome
AF:
0.0000567
AC:
78
AN:
1376296
Hom.:
0
Cov.:
35
AF XY:
0.0000619
AC XY:
42
AN XY:
678484
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000288
Gnomad4 ASJ exome
AF:
0.00189
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000167
Gnomad4 OTH exome
AF:
0.000191
GnomAD4 genome
AF:
0.0000723
AC:
11
AN:
152208
Hom.:
0
Cov.:
34
AF XY:
0.000108
AC XY:
8
AN XY:
74360
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00259
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000347
Hom.:
0
Bravo
AF:
0.0000378
ExAC
AF:
0.000132
AC:
2

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Dec 02, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.977G>A (p.G326D) alteration is located in exon 1 (coding exon 1) of the ANKRD63 gene. This alteration results from a G to A substitution at nucleotide position 977, causing the glycine (G) at amino acid position 326 to be replaced by an aspartic acid (D). 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
Uncertain
0.39
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.29
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.0085
T
Eigen
Benign
-0.13
Eigen_PC
Benign
-0.077
FATHMM_MKL
Uncertain
0.76
D
LIST_S2
Benign
0.54
T
M_CAP
Benign
0.061
D
MetaRNN
Benign
0.027
T
MetaSVM
Benign
-0.90
T
MutationAssessor
Benign
0.0
N
PrimateAI
Uncertain
0.78
T
PROVEAN
Benign
-1.1
N
REVEL
Benign
0.22
Sift
Pathogenic
0.0
D
Sift4G
Uncertain
0.010
D
Vest4
0.20
MutPred
0.28
Loss of sheet (P = 0.0228);
MVP
0.40
ClinPred
0.16
T
GERP RS
2.7
Varity_R
0.33
gMVP
0.096

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs749361049; hg19: chr15-40573811; API