Variant chr19-4207960-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001393985.1(ANKRD24):c.824C>A(p.Pro275Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000527 in 1,499,352 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000053 ( 0 hom. )

Consequence

ANKRD24
NM_001393985.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.692

Variant links:

Genes affected

ANKRD24 (HGNC:29424): (ankyrin repeat domain 24)

ANKRD24 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10007888).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKRD24	NM_001393985.1 linkuse as main transcript	c.824C>A	p.Pro275Gln	missense_variant	10/22	ENST00000318934.9	NP_001380914.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ANKRD24	ENST00000318934.9 linkuse as main transcript	c.824C>A	p.Pro275Gln	missense_variant	10/22	5	NM_001393985.1	ENSP00000321731.4	Q8TF21-1
ANKRD24	ENST00000597689.5 linkuse as main transcript	c.737C>A	p.Pro246Gln	missense_variant	8/16	1		ENSP00000470227.1	M0QZ18
ANKRD24	ENST00000262970.9 linkuse as main transcript	c.1094C>A	p.Pro365Gln	missense_variant	8/20	5		ENSP00000262970.4	Q8TF21-2
ANKRD24	ENST00000600132.5 linkuse as main transcript	c.824C>A	p.Pro275Gln	missense_variant	10/22	5		ENSP00000471252.1	Q8TF21-1

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000746

AC:

AN:

134082

Hom.:

AF XY:

0.0000841

AC XY:

AN XY:

71350

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000656

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000140

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000534

AC:

AN:

1347122

Hom.:

Cov.:

AF XY:

0.0000501

AC XY:

AN XY:

659118

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000402

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000149

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000642

Gnomad4 OTH exome

AF:

0.0000361

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152230

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000991

Hom.:

Bravo

AF:

0.0000416

ExAC

AF:

0.0000419

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 03, 2024

The c.824C>A (p.P275Q) alteration is located in exon 10 (coding exon 9) of the ANKRD24 gene. This alteration results from a C to A substitution at nucleotide position 824, causing the proline (P) at amino acid position 275 to be replaced by a glutamine (Q). 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

Benign

0.099

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0026

T;T;T;.

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.63

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.74

.;T;T;T

M_CAP

Benign

0.015

MetaRNN

Benign

0.10

T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.8

L;L;.;.

PrimateAI

Benign

0.45

PROVEAN

Benign

-1.9

.;N;.;N

REVEL

Benign

0.072

Sift

Uncertain

0.012

.;D;.;D

Sift4G

Benign

0.50

T;T;T;T

Polyphen

0.70

P;P;.;D

Vest4

0.30

MVP

0.30

MPC

0.29

ClinPred

0.058

GERP RS

-1.7

Varity_R

0.053

gMVP

0.21

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over