chr15-40282221-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001190479.3(ANKRD63):​c.366G>A​(p.Met122Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

ANKRD63
NM_001190479.3 missense

Scores

3
4
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.35
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 Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ANKRD63NM_001190479.3 linkc.366G>A p.Met122Ile 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.366G>A p.Met122Ile missense_variant Exon 1 of 1 6 NM_001190479.3 ENSP00000399547.1 C9JTQ0
PLCB2ENST00000560009.1 linkn.394+2218G>A intron_variant Intron 2 of 2 4

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1361618
Hom.:
0
Cov.:
35
AF XY:
0.00
AC XY:
0
AN XY:
671916
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
34

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Aug 27, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.366G>A (p.M122I) 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 366, causing the methionine (M) at amino acid position 122 to be replaced by an isoleucine (I). 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
0.95
BayesDel_addAF
Uncertain
0.077
D
BayesDel_noAF
Benign
-0.13
CADD
Uncertain
24
DANN
Uncertain
0.98
DEOGEN2
Benign
0.018
T
Eigen
Benign
0.059
Eigen_PC
Benign
0.11
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Benign
0.51
T
M_CAP
Pathogenic
0.83
D
MetaRNN
Uncertain
0.69
D
MetaSVM
Benign
-0.84
T
MutationAssessor
Benign
0.29
N
PrimateAI
Pathogenic
0.97
D
PROVEAN
Benign
-1.4
N
REVEL
Benign
0.26
Sift
Benign
0.25
T
Sift4G
Benign
0.47
T
Vest4
0.60
MutPred
0.63
Loss of disorder (P = 0.1261);
MVP
0.39
ClinPred
0.49
T
GERP RS
3.6
Varity_R
0.21
gMVP
0.69

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-40574422; API