Variant 11-83224945-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000533342.6(ANKRD42):c.677A>G(p.Asn226Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00007 in 1,613,646 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000065 ( 0 hom. )

Consequence

ANKRD42
ENST00000533342.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.73

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKRD42	NM_001300975.2 linkuse as main transcript	c.677A>G	p.Asn226Ser	missense_variant	6/11	ENST00000533342.6	NP_001287904.1	Q8N9B4E9PIL2
ANKRD42	NM_001300973.2 linkuse as main transcript	c.674A>G	p.Asn225Ser	missense_variant	6/12		NP_001287902.1	Q8N9B4F8W6I9A1DRY3
ANKRD42	NM_001300972.2 linkuse as main transcript	c.677A>G	p.Asn226Ser	missense_variant	6/12		NP_001287901.1	Q8N9B4E9PP91A1XPJ0
ANKRD42	NM_182603.4 linkuse as main transcript	c.593A>G	p.Asn198Ser	missense_variant	6/10		NP_872409.2	Q8N9B4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ANKRD42	ENST00000533342.6 linkuse as main transcript	c.677A>G	p.Asn226Ser	missense_variant	6/11	1	NM_001300975.2	ENSP00000435790.1	E9PIL2
ANKRD42	ENST00000260047.10 linkuse as main transcript	c.674A>G	p.Asn225Ser	missense_variant	6/12	1		ENSP00000260047.6	F8W6I9
ANKRD42	ENST00000531895.5 linkuse as main transcript	c.677A>G	p.Asn226Ser	missense_variant	6/12	1		ENSP00000434666.1	E9PP91
ANKRD42	ENST00000393392.6 linkuse as main transcript	c.593A>G	p.Asn198Ser	missense_variant	6/10	2		ENSP00000377051.2	Q8N9B4-1

Frequencies

GnomAD3 genomes

AF:

0.000118

AC:

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

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:

0.000147

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000995

AC:

AN:

251352

Hom.:

AF XY:

0.0000810

AC XY:

AN XY:

135828

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000202

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000106

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.0000650

AC:

AN:

1461290

Hom.:

Cov.:

AF XY:

0.0000619

AC XY:

AN XY:

726978

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000246

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000684

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.000118

AC:

AN:

152356

Hom.:

Cov.:

AF XY:

0.0000805

AC XY:

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.0000962

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000148

Hom.:

Bravo

AF:

0.0000831

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000988

AC:

EpiCase

AF:

0.0000546

EpiControl

AF:

0.000119

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

Oct 04, 2022

The c.593A>G (p.N198S) alteration is located in exon 6 (coding exon 6) of the ANKRD42 gene. This alteration results from a A to G substitution at nucleotide position 593, causing the asparagine (N) at amino acid position 198 to be replaced by a serine (S). 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

0.28

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.40

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.052

.;.;T;.

Eigen

Uncertain

0.67

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.93

D;D;D;D

M_CAP

Benign

0.012

MetaRNN

Uncertain

0.55

D;D;D;D

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.8

.;.;M;.

MutationTaster

Benign

0.99

D;D;D;D

PrimateAI

Uncertain

0.51

PROVEAN

Uncertain

-3.6

D;D;D;D

REVEL

Benign

0.24

Sift

Uncertain

0.0060

D;D;T;D

Sift4G

Uncertain

0.036

D;D;D;D

Polyphen

1.0, 1.0

.;.;D;D

Vest4

0.70

MVP

0.67

MPC

0.53

ClinPred

0.50

GERP RS

5.7

Varity_R

0.29

gMVP

0.29

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