chr15-40281769-C-T

Variant names:

• chr15-40281769-C-T
• NM_001190479.3:c.818G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001190479.3(ANKRD63):​c.818G>A​(p.Arg273Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000145 in 1,382,754 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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: 0.0000014 (0 hom.)
• Consequence: ANKRD63 NM_001190479.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.31
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19348362).

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.818G>A	p.Arg273Gln	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.818G>A	p.Arg273Gln	missense	Exon 1 of 1	ENSP00000399547.1	C9JTQ0
	PLCB2	ENST00000560009.1	TSL:4	n.394+2670G>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000145 AC: 2 AN: 1382754 Hom.: 0 Cov.: 35 AF XY: 0.00000147 AC XY: 1 AN XY: 682306

African (AFR) AF: 0.00 AC: 0 AN: 31558

American (AMR) AF: 0.00 AC: 0 AN: 35662

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25140

East Asian (EAS) AF: 0.00 AC: 0 AN: 35694

South Asian (SAS) AF: 0.00 AC: 0 AN: 79182

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33436

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5688

European-Non Finnish (NFE) AF: 0.00000185 AC: 2 AN: 1078534

Other (OTH) AF: 0.00 AC: 0 AN: 57860

GnomAD4 genome Cov.: 34

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.45
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0071	T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.70	T
M_CAP	Uncertain	0.098	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		2.3
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-0.48	N
REVEL	Benign	0.078
Sift	Uncertain	0.0020	D
Sift4G	Benign	0.51	T
Vest4		0.29
MutPred		0.53		Loss of MoRF binding (P = 0.0729)
MVP		0.21
ClinPred		0.72	D
GERP RS		3.5
Varity_R		0.12
gMVP		0.35
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

hg19: chr15-40573970;