11-83206073-C-G

Variant names:

• chr11-83206073-C-G
• rs201130789
• NM_001300975.2:c.238C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001300975.2(ANKRD42):​c.238C>G​(p.Leu80Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. L80I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000096 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ANKRD42 NM_001300975.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.02
• Publications: 1 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.013875961).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD42	NM_001300975.2	MANE Select	c.238C>G	p.Leu80Val	missense	Exon 3 of 11	NP_001287904.1	E9PIL2
	ANKRD42	NM_001433541.1		c.238C>G	p.Leu80Val	missense	Exon 3 of 13	NP_001420470.1
	ANKRD42	NM_001300973.2		c.238C>G	p.Leu80Val	missense	Exon 3 of 12	NP_001287902.1	F8W6I9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD42	ENST00000533342.6	TSL:1 MANE Select	c.238C>G	p.Leu80Val	missense	Exon 3 of 11	ENSP00000435790.1	E9PIL2
	ANKRD42	ENST00000260047.10	TSL:1	c.238C>G	p.Leu80Val	missense	Exon 3 of 12	ENSP00000260047.6	F8W6I9
	ANKRD42	ENST00000531895.5	TSL:1	c.238C>G	p.Leu80Val	missense	Exon 3 of 12	ENSP00000434666.1	E9PP91

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.000290 AC: 72 AN: 248336 AF XY: 0.000238

Gnomad AFR exome AF: 0.000449

Gnomad AMR exome AF: 0.0000292

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000827

Gnomad FIN exome AF: 0.000752

Gnomad NFE exome AF: 0.000249

Gnomad OTH exome AF: 0.000166

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000959 AC: 14 AN: 1460248 Hom.: 0 Cov.: 30 AF XY: 0.00000964 AC XY: 7 AN XY: 726426

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33450

American (AMR) AF: 0.00 AC: 0 AN: 44588

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86178

European-Finnish (FIN) AF: 0.000171 AC: 9 AN: 52732

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111496

Other (OTH) AF: 0.0000498 AC: 3 AN: 60240

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ExAC AF: 0.00198 AC: 240

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Uncertain	0.026	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.015	T
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.83	T
MetaRNN	Benign	0.014	T
MetaSVM	Uncertain	-0.26	T
MutationAssessor	Benign	1.5	L
PhyloP100		4.0
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.14
Sift	Benign	0.082	T
Sift4G	Benign	0.093	T
Polyphen		1.0	D
Vest4		0.67
MVP		0.61
MPC		0.46
ClinPred		0.030	T
GERP RS		5.7
Varity_R		0.23
gMVP		0.32
Mutation Taster		=269/31	polymorphism

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

Other links and lift over

dbSNP: rs201130789; hg19: chr11-82917115;