11-83194726-C-T

Variant names:

• chr11-83194726-C-T
• rs1342810881
• NM_001300975.2:c.56C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001300975.2(ANKRD42):​c.56C>T​(p.Pro19Leu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,172 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/24 in silico tools predict a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: ANKRD42 NM_001300975.2 missense, splice_region
• Scores: Splicing: ADA: 0.9744
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.79
• Publications: 0 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1049729).

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.56C>T	p.Pro19Leu	missense splice_region	Exon 1 of 11	NP_001287904.1	E9PIL2
	ANKRD42	NM_001433541.1		c.56C>T	p.Pro19Leu	missense splice_region	Exon 1 of 13	NP_001420470.1
	ANKRD42	NM_001300973.2		c.56C>T	p.Pro19Leu	missense splice_region	Exon 1 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.56C>T	p.Pro19Leu	missense splice_region	Exon 1 of 11	ENSP00000435790.1	E9PIL2
	ANKRD42	ENST00000260047.10	TSL:1	c.56C>T	p.Pro19Leu	missense splice_region	Exon 1 of 12	ENSP00000260047.6	F8W6I9
	ANKRD42	ENST00000531895.5	TSL:1	c.56C>T	p.Pro19Leu	missense splice_region	Exon 1 of 12	ENSP00000434666.1	E9PP91

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152172 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152172 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74354

African (AFR) AF: 0.00 AC: 0 AN: 41440

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.032	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0029	T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.18	N
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.2	L
PhyloP100		2.8
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.24	N
REVEL	Benign	0.083
Sift	Benign	0.29	T
Sift4G	Benign	0.14	T
Polyphen		0.034	B
Vest4		0.26
MutPred		0.31		Loss of catalytic residue at P19 (P = 0.0244)
MVP		0.56
MPC		0.15
ClinPred		0.52	D
GERP RS		3.5
PromoterAI		0.061	Neutral
Varity_R		0.067
gMVP		0.27
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	0.97
dbscSNV1_RF	Benign	0.58
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

Other links and lift over

dbSNP: rs1342810881; hg19: chr11-82905768;