Genetic Variant ANKRD63:p.Arg138Gln (chr15-40282174-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001190479.3(ANKRD63):c.413G>A(p.Arg138Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000746 in 1,341,046 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 7.5e-7 ( 0 hom. )

Consequence

ANKRD63
NM_001190479.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.06

Publications

0 publications found

Variant links:

Genes affected

ANKRD63 (HGNC:40027): (ankyrin repeat domain 63)

ANKRD63 links:

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]

PLCB2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2900874).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001190479.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD63	NM_001190479.3	MANE Select	c.413G>A	p.Arg138Gln	missense	Exon 1 of 1	NP_001177408.1	C9JTQ0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD63	ENST00000434396.2	TSL:6 MANE Select	c.413G>A	p.Arg138Gln	missense	Exon 1 of 1	ENSP00000399547.1	C9JTQ0
	PLCB2	ENST00000560009.1	TSL:4	n.394+2265G>A		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.46e-7

AC:

AN:

1341046

Hom.:

Cov.:

AF XY:

0.00000151

AC XY:

AN XY:

660960

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

27008

American (AMR)

AF:

0.00

AC:

AN:

29464

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23480

East Asian (EAS)

AF:

0.00

AC:

AN:

30742

South Asian (SAS)

AF:

0.00

AC:

AN:

74568

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32974

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4652

European-Non Finnish (NFE)

AF:

9.41e-7

AC:

AN:

1062284

Other (OTH)

AF:

0.00

AC:

AN:

55874

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.38

BayesDel_addAF

Benign

-0.045

BayesDel_noAF

Benign

-0.30

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0056

Eigen

Benign

0.022

Eigen_PC

Benign

0.092

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.86

M_CAP

Pathogenic

0.83

MetaRNN

Benign

0.29

MetaSVM

Benign

-0.79

MutationAssessor

Benign

0.98

PhyloP100

3.1

PrimateAI

Pathogenic

0.95

PROVEAN

Benign

-0.14

REVEL

Benign

0.094

Sift

Benign

0.078

Sift4G

Benign

0.59

Vest4

0.28

MutPred

0.33

Loss of MoRF binding (P = 0.0278)

MVP

0.33

ClinPred

0.85

GERP RS

3.5

Varity_R

0.15

gMVP

0.31

Mutation Taster

=67/33

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over