11-83211304-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001300975.2(ANKRD42):c.460G>A(p.Val154Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ANKRD42 NM_001300975.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.746

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]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.094620466).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKRD42	NM_001300975.2	c.460G>A	p.Val154Met	missense_variant	5/11	ENST00000533342.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKRD42	ENST00000533342.6	c.460G>A	p.Val154Met	missense_variant	5/11	1	NM_001300975.2	A2
	ENST00000531869.1	n.91-1198C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 20, 2022

The c.376G>A (p.V126M) alteration is located in exon 5 (coding exon 5) of the ANKRD42 gene. This alteration results from a G to A substitution at nucleotide position 376, causing the valine (V) at amino acid position 126 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.050	T
BayesDel_noAF	Benign	-0.31
Cadd	Benign	13
Dann	Uncertain	0.99
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.082	N
LIST_S2	Benign	0.81	T;T;T;T;T;T;T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.095	T;T;T;T;T;T;T
MetaSVM	Benign	-0.77	T
MutationTaster	Benign	1.0	N;N;N;N;N;N;N
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.6	N;N;N;N;N;N;N
REVEL	Benign	0.036
Sift	Benign	0.23	T;D;T;T;T;T;T
Sift4G	Benign	0.061	T;D;T;T;T;T;T
Polyphen		0.033	B;.;.;.;.;B;B
Vest4		0.18
MutPred		0.59		Gain of disorder (P = 0.0897);.;.;Gain of disorder (P = 0.0897);Gain of disorder (P = 0.0897);.;Gain of disorder (P = 0.0897);
MVP		0.61
MPC		0.27
ClinPred		0.20	T
GERP RS		2.0
Varity_R		0.034
gMVP		0.18

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-82922346;