Variant 19-4199764-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001393985.1(ANKRD24):c.118C>T(p.Arg40Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000976 in 1,536,780 control chromosomes in the GnomAD database, including 1 homozygotes. 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: 𝑓 0.000033 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0000072 ( 0 hom. )

Consequence

ANKRD24
NM_001393985.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.267

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.043598473).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKRD24	NM_001393985.1 linkuse as main transcript	c.118C>T	p.Arg40Cys	missense_variant	3/22	ENST00000318934.9	NP_001380914.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKRD24	ENST00000318934.9 linkuse as main transcript	c.118C>T	p.Arg40Cys	missense_variant	3/22	5	NM_001393985.1	ENSP00000321731	A2	Q8TF21-1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152208

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:

0.000386

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000224

AC:

AN:

134146

Hom.:

AF XY:

0.0000274

AC XY:

AN XY:

72892

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000951

Gnomad SAS exome

AF:

0.0000450

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000198

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000722

AC:

AN:

1384456

Hom.:

Cov.:

AF XY:

0.00000586

AC XY:

AN XY:

682596

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000281

Gnomad4 SAS exome

AF:

0.0000254

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000372

Gnomad4 OTH exome

AF:

0.0000521

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152324

Hom.:

Cov.:

AF XY:

0.0000268

AC XY:

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00142

Bravo

AF:

0.0000151

ExAC

AF:

0.0000217

AC:

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

Mar 20, 2023

The c.118C>T (p.R40C) alteration is located in exon 3 (coding exon 2) of the ANKRD24 gene. This alteration results from a C to T substitution at nucleotide position 118, causing the arginine (R) at amino acid position 40 to be replaced by a cysteine (C). 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

0.18

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0026

T;T

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.50

LIST_S2

Benign

0.52

.;T

M_CAP

Benign

0.050

MetaRNN

Benign

0.044

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

N;N

MutationTaster

Benign

1.0

D;N

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.97

.;N

REVEL

Benign

0.022

Sift

Benign

0.24

.;T

Sift4G

Benign

0.21

T;T

Polyphen

0.013

B;B

Vest4

0.20

MutPred

0.36

Loss of MoRF binding (P = 0.0056);Loss of MoRF binding (P = 0.0056);

MVP

0.099

MPC

0.35

ClinPred

0.062

GERP RS

0.82

Varity_R

0.066

gMVP

0.44

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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