Genetic Variant ANKRD42:p.Arg125Gly (chr11-83210342-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001300975.2(ANKRD42):c.373C>G(p.Arg125Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,612 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R125W) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ANKRD42
NM_001300975.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.294

Publications

4 publications found

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:

ENSG00000254551 (HGNC:):

ENSG00000254551 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.39387208).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001300975.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ANKRD42	NM_001300975.2	MANE Select	c.373C>G	p.Arg125Gly	missense	Exon 4 of 11	NP_001287904.1	E9PIL2
ANKRD42	NM_001433541.1		c.373C>G	p.Arg125Gly	missense	Exon 4 of 13	NP_001420470.1
ANKRD42	NM_001300973.2		c.373C>G	p.Arg125Gly	missense	Exon 4 of 12	NP_001287902.1	F8W6I9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ANKRD42	ENST00000533342.6	TSL:1 MANE Select	c.373C>G	p.Arg125Gly	missense	Exon 4 of 11	ENSP00000435790.1	E9PIL2
ANKRD42	ENST00000260047.10	TSL:1	c.373C>G	p.Arg125Gly	missense	Exon 4 of 12	ENSP00000260047.6	F8W6I9
ANKRD42	ENST00000531895.5	TSL:1	c.373C>G	p.Arg125Gly	missense	Exon 4 of 12	ENSP00000434666.1	E9PP91

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461612

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727114

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33472

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39668

South Asian (SAS)

AF:

0.00

AC:

AN:

86248

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53406

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1111820

Other (OTH)

AF:

0.00

AC:

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Uncertain

0.010

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.064

Eigen

Uncertain

0.22

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Benign

0.69

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.058

MetaRNN

Benign

0.39

MetaSVM

Uncertain

-0.17

MutationAssessor

Benign

0.55

PhyloP100

0.29

PrimateAI

Benign

0.44

PROVEAN

Pathogenic

-4.4

REVEL

Benign

0.20

Sift

Uncertain

0.013

Sift4G

Benign

0.30

Polyphen

1.0

Vest4

0.49

MutPred

0.45

Gain of catalytic residue at C127 (P = 0.0896)

MVP

0.84

MPC

0.58

ClinPred

0.96

GERP RS

5.0

Varity_R

0.38

gMVP

0.27

Mutation Taster

=76/24

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over