11-83210388-T-C

Variant summary

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

The NM_001300975.2(ANKRD42):c.419T>C(p.Phe140Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ANKRD42 NM_001300975.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.20

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKRD42	NM_001300975.2	c.419T>C	p.Phe140Ser	missense_variant	4/11	ENST00000533342.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKRD42	ENST00000533342.6	c.419T>C	p.Phe140Ser	missense_variant	4/11	1	NM_001300975.2	A2
	ENST00000531869.1	n.91-282A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

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 28, 2022

The c.335T>C (p.F112S) alteration is located in exon 4 (coding exon 4) of the ANKRD42 gene. This alteration results from a T to C substitution at nucleotide position 335, causing the phenylalanine (F) at amino acid position 112 to be replaced by a serine (S). 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	Uncertain	0.54
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
Cadd	Benign	23
Dann	Uncertain	1.0
Eigen	Benign	-0.14
Eigen_PC	Benign	0.079
FATHMM_MKL	Benign	0.73	D
LIST_S2	Uncertain	0.86	D;D;D;D;D;D;D
M_CAP	Benign	0.045	D
MetaRNN	Uncertain	0.45	T;T;T;T;T;T;T
MetaSVM	Benign	-0.55	T
MutationTaster	Benign	0.72	D;D;D;D;D;D;D
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-3.4	D;D;D;D;D;D;D
REVEL	Benign	0.28
Sift	Benign	0.20	T;T;T;T;T;T;T
Sift4G	Benign	0.40	T;T;T;T;T;T;T
Polyphen		0.13	B;.;.;.;.;P;B
Vest4		0.64
MutPred		0.48		Gain of disorder (P = 9e-04);.;Gain of disorder (P = 9e-04);Gain of disorder (P = 9e-04);Gain of disorder (P = 9e-04);.;Gain of disorder (P = 9e-04);
MVP		0.76
MPC		0.77
ClinPred		0.97	D
GERP RS		4.7
Varity_R		0.23
gMVP		0.30

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-82921430;