Genetic Variant ANKRD63:p.Asn365Lys (chr15-40281492-G-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001190479.3(ANKRD63):c.1095C>A(p.Asn365Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000767 in 1,303,026 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 7.7e-7 ( 0 hom. )

Consequence

ANKRD63
NM_001190479.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.578

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: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.035969228).

BP6

Variant 15-40281492-G-T is Benign according to our data. Variant chr15-40281492-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3873983.Status of the report is criteria_provided_single_submitter, 1 stars.

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.1095C>A	p.Asn365Lys	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.1095C>A	p.Asn365Lys	missense	Exon 1 of 1	ENSP00000399547.1	C9JTQ0
	PLCB2	ENST00000560009.1	TSL:4	n.394+2947C>A		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.67e-7

AC:

AN:

1303026

Hom.:

Cov.:

AF XY:

0.00000157

AC XY:

AN XY:

635034

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28202

American (AMR)

AF:

0.00

AC:

AN:

22716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20466

East Asian (EAS)

AF:

0.00

AC:

AN:

33704

South Asian (SAS)

AF:

0.00

AC:

AN:

67894

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31158

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4540

European-Non Finnish (NFE)

AF:

9.61e-7

AC:

AN:

1040212

Other (OTH)

AF:

0.00

AC:

AN:

54134

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Likely benign

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

Benign

0.20

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.73

CADD

Benign

7.1

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.0027

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.36

M_CAP

Benign

0.0050

MetaRNN

Benign

0.036

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.34

PhyloP100

0.58

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.070

REVEL

Benign

0.011

Sift

Benign

0.97

Sift4G

Benign

0.29

Vest4

0.067

MutPred

0.22

Gain of methylation at N365 (P = 0.003)

MVP

0.092

ClinPred

0.082

GERP RS

2.8

Varity_R

0.046

gMVP

0.057

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over