11-83211331-G-T

Variant names:

• chr11-83211331-G-T
• rs919305719
• NM_001300975.2:c.487G>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001300975.2(ANKRD42):​c.487G>T​(p.Val163Leu) 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.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ANKRD42 NM_001300975.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.53

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]

ENSG00000254551 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27430338).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD42	NM_001300975.2	c.487G>T	p.Val163Leu	missense_variant	Exon 5 of 11	ENST00000533342.6	NP_001287904.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKRD42	ENST00000533342.6	c.487G>T	p.Val163Leu	missense_variant	Exon 5 of 11	1	NM_001300975.2	ENSP00000435790.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0018	.;.;.;.;.;T;.
Eigen	Benign	0.088
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.88	D;D;D;D;D;D;D
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.27	T;T;T;T;T;T;T
MetaSVM	Benign	-0.44	T
MutationAssessor	Benign	-1.9	.;.;.;.;.;N;.
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.82	N;N;N;N;N;N;N
REVEL	Benign	0.17
Sift	Benign	1.0	T;T;T;T;T;T;T
Sift4G	Benign	0.91	T;T;T;T;T;T;T
Polyphen		0.41	B;.;.;.;.;D;P
Vest4		0.54
MutPred		0.60		Loss of disorder (P = 0.2116);.;.;Loss of disorder (P = 0.2116);Loss of disorder (P = 0.2116);.;Loss of disorder (P = 0.2116);
MVP		0.63
MPC		0.59
ClinPred		0.92	D
GERP RS		5.7
Varity_R		0.22
gMVP		0.17

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

Publications

LitVar

Other links and lift over

dbSNP: rs919305719; hg19: chr11-82922373;