Variant 11-83227816-A-T 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_001300975.2(ANKRD42):c.857A>T(p.Asp286Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000267 in 1,613,508 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

ANKRD42
NM_001300975.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.74

Variant links:

Genes affected

ANKRD42 (HGNC:26752): (ankyrin repeat domain 42) Predicted to enable NF-kappaB binding activity. Predicted to act upstream of or within positive regulation of NF-kappaB transcription factor activity and positive regulation of cytokine production involved in inflammatory response. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ANKRD42 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=0.24197441).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ANKRD42	NM_001300975.2 linkuse as main transcript	c.857A>T	p.Asp286Val	missense_variant	7/11	ENST00000533342.6
ANKRD42	NM_001300973.2 linkuse as main transcript	c.854A>T	p.Asp285Val	missense_variant	7/12
ANKRD42	NM_001300972.2 linkuse as main transcript	c.857A>T	p.Asp286Val	missense_variant	7/12
ANKRD42	NM_182603.4 linkuse as main transcript	c.773A>T	p.Asp258Val	missense_variant	7/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKRD42	ENST00000533342.6 linkuse as main transcript	c.857A>T	p.Asp286Val	missense_variant	7/11	1	NM_001300975.2	A2

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152186

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:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000199

AC:

AN:

251010

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135668

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000199

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000253

AC:

AN:

1461322

Hom.:

Cov.:

AF XY:

0.0000248

AC XY:

AN XY:

726966

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000766

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000297

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152186

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74332

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:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000450

Hom.:

Bravo

AF:

0.0000340

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000412

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

Nov 01, 2022

The c.773A>T (p.D258V) alteration is located in exon 7 (coding exon 7) of the ANKRD42 gene. This alteration results from a A to T substitution at nucleotide position 773, causing the aspartic acid (D) at amino acid position 258 to be replaced by a valine (V). 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

0.13

BayesDel_addAF

Benign

-0.038

BayesDel_noAF

Benign

-0.14

Cadd

Uncertain

Dann

Uncertain

0.98

Eigen

Uncertain

0.22

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Benign

0.69

LIST_S2

Uncertain

0.91

D;D;D;D;D

M_CAP

Uncertain

0.096

MetaRNN

Benign

0.24

T;T;T;T;T

MetaSVM

Uncertain

-0.25

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Benign

0.40

PROVEAN

Uncertain

-3.8

D;D;D;D;D

REVEL

Benign

0.27

Sift

Uncertain

0.018

D;D;T;T;T

Sift4G

Benign

0.15

T;T;T;T;T

Polyphen

0.83

.;.;P;P;.

Vest4

0.48

MVP

0.86

MPC

0.63

ClinPred

0.31

GERP RS

4.2

Varity_R

0.24

gMVP

0.40

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