Genetic Variant NM_001300975.2:c.230A>G (chr11-83206065-A-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001300975.2(ANKRD42):c.230A>G(p.His77Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,708 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. H77L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ANKRD42
NM_001300975.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.67

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.230A>G	p.His77Arg	missense	Exon 3 of 11	NP_001287904.1	E9PIL2
ANKRD42	NM_001433541.1		c.230A>G	p.His77Arg	missense	Exon 3 of 13	NP_001420470.1
ANKRD42	NM_001300973.2		c.230A>G	p.His77Arg	missense	Exon 3 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.230A>G	p.His77Arg	missense	Exon 3 of 11	ENSP00000435790.1	E9PIL2
ANKRD42	ENST00000260047.10	TSL:1	c.230A>G	p.His77Arg	missense	Exon 3 of 12	ENSP00000260047.6	F8W6I9
ANKRD42	ENST00000531895.5	TSL:1	c.230A>G	p.His77Arg	missense	Exon 3 of 12	ENSP00000434666.1	E9PP91

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460708

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726708

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33440

American (AMR)

AF:

0.00

AC:

AN:

44514

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26104

East Asian (EAS)

AF:

0.00

AC:

AN:

39682

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86148

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53370

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111332

Other (OTH)

AF:

0.00

AC:

AN:

60354

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.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.43

BayesDel_addAF

Pathogenic

0.25

BayesDel_noAF

Uncertain

0.12

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.023

Eigen

Uncertain

0.30

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.81

M_CAP

Benign

0.023

MetaRNN

Uncertain

0.43

MetaSVM

Benign

-0.67

MutationAssessor

Benign

-0.57

PhyloP100

6.7

PrimateAI

Uncertain

0.60

PROVEAN

Uncertain

-3.3

REVEL

Uncertain

0.31

Sift

Benign

0.19

Sift4G

Benign

0.19

Polyphen

0.96

Vest4

0.63

MutPred

0.45

Gain of MoRF binding (P = 0.0755)

MVP

0.61

MPC

0.63

ClinPred

0.98

GERP RS

5.7

Varity_R

0.36

gMVP

0.28

Mutation Taster

=231/69

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