11-83206073-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001300975.2(ANKRD42):​c.238C>T​(p.Leu80Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000479 in 1,460,296 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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: 0.0000048 (0 hom.)
• 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: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.832

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>T	p.Leu80Phe	missense	Exon 3 of 11	NP_001287904.1	E9PIL2
	ANKRD42	NM_001433541.1		c.238C>T	p.Leu80Phe	missense	Exon 3 of 13	NP_001420470.1
	ANKRD42	NM_001300973.2		c.238C>T	p.Leu80Phe	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>T	p.Leu80Phe	missense	Exon 3 of 11	ENSP00000435790.1	E9PIL2
	ANKRD42	ENST00000260047.10	TSL:1	c.238C>T	p.Leu80Phe	missense	Exon 3 of 12	ENSP00000260047.6	F8W6I9
	ANKRD42	ENST00000531895.5	TSL:1	c.238C>T	p.Leu80Phe	missense	Exon 3 of 12	ENSP00000434666.1	E9PP91

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000805 AC: 2 AN: 248336 AF XY: 0.0000149

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000178

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1460296 Hom.: 0 Cov.: 30 AF XY: 0.00000688 AC XY: 5 AN XY: 726448

African (AFR) AF: 0.00 AC: 0 AN: 33452

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: 0.0000348 AC: 3 AN: 86178

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52772

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

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111500

Other (OTH) AF: 0.0000166 AC: 1 AN: 60242

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.53
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.11	T
Eigen	Pathogenic	0.75
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.076	D
MetaRNN	Pathogenic	0.83	D
MetaSVM	Uncertain	0.22	D
MutationAssessor	Uncertain	2.6	M
PhyloP100		4.0
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.20
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0070	D
Polyphen		1.0	D
Vest4		0.82
MutPred		0.59		Gain of catalytic residue at L80 (P = 0.0312)
MVP		0.68
MPC		0.61
ClinPred		0.92	D
GERP RS		5.7
Varity_R		0.35
gMVP		0.42
Mutation Taster		=269/31	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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;