Variant chr19-4199738-T-C 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.92T>C(p.Ile31Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000273 in 1,537,926 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: 𝑓 0.00025 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00028 ( 0 hom. )

Consequence

ANKRD24
NM_001393985.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.263

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=0.15113714).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKRD24	NM_001393985.1 linkuse as main transcript	c.92T>C	p.Ile31Thr	missense_variant	3/22	ENST00000318934.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKRD24	ENST00000318934.9 linkuse as main transcript	c.92T>C	p.Ile31Thr	missense_variant	3/22	5	NM_001393985.1	A2	Q8TF21-1

Frequencies

GnomAD3 genomes

AF:

0.000250

AC:

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00151

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:

0.000176

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000126

AC:

AN:

135268

Hom.:

AF XY:

0.0000817

AC XY:

AN XY:

73460

show subpopulations

Gnomad AFR exome

AF:

0.000153

Gnomad AMR exome

AF:

0.000455

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:

0.0000984

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000276

AC:

382

AN:

1385784

Hom.:

Cov.:

AF XY:

0.000249

AC XY:

170

AN XY:

683292

show subpopulations

Gnomad4 AFR exome

AF:

0.0000636

Gnomad4 AMR exome

AF:

0.000254

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000327

Gnomad4 OTH exome

AF:

0.000330

GnomAD4 genome

AF:

0.000250

AC:

AN:

152142

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.00151

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.000215

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 18, 2023

The c.92T>C (p.I31T) alteration is located in exon 3 (coding exon 2) of the ANKRD24 gene. This alteration results from a T to C substitution at nucleotide position 92, causing the isoleucine (I) at amino acid position 31 to be replaced by a threonine (T). 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

Pathogenic

0.89

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0018

T;T

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.29

FATHMM_MKL

Benign

0.37

M_CAP

Benign

0.020

MetaRNN

Benign

0.15

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

N;N

MutationTaster

Benign

1.0

D;N

PrimateAI

Pathogenic

0.81

Sift4G

Uncertain

0.031

D;D

Polyphen

0.60

P;P

Vest4

0.61

MutPred

0.39

Gain of glycosylation at I31 (P = 0.0011);Gain of glycosylation at I31 (P = 0.0011);

MVP

0.31

MPC

0.64

ClinPred

0.029

GERP RS

2.2

Varity_R

0.087

gMVP

0.18

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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