rs576666131

Variant names:

• chr11-83210397-A-G
• rs576666131
• NM_001300975.2:c.428A>G

Your query was ambiguous. Multiple possible variants found:

• chr11-83210397-A-G
• chr11-83210397-A-T

Variant summary

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

The NM_001300975.2(ANKRD42):​c.428A>G​(p.Gln143Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000479 in 1,461,674 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: ANKRD42 NM_001300975.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.78

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD42	NM_001300975.2	c.428A>G	p.Gln143Arg	missense_variant	Exon 4 of 11	ENST00000533342.6	NP_001287904.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKRD42	ENST00000533342.6	c.428A>G	p.Gln143Arg	missense_variant	Exon 4 of 11	1	NM_001300975.2	ENSP00000435790.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251458 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135900

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 SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461674 Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3 AN XY: 727148

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000630

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.067	.;.;.;.;.;T;.
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.80	T;T;T;T;T;T;T
M_CAP	Benign	0.026	D
MetaRNN	Uncertain	0.62	D;D;D;D;D;D;D
MetaSVM	Uncertain	-0.22	T
MutationAssessor	Benign	-0.33	.;.;.;.;.;N;.
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-2.6	D;D;D;D;N;D;D
REVEL	Uncertain	0.32
Sift	Uncertain	0.019	D;D;T;D;T;T;T
Sift4G	Benign	0.40	T;T;T;T;T;T;T
Polyphen		0.96	D;.;.;.;.;D;D
Vest4		0.63
MutPred		0.47		Gain of MoRF binding (P = 0.0673);.;Gain of MoRF binding (P = 0.0673);Gain of MoRF binding (P = 0.0673);Gain of MoRF binding (P = 0.0673);.;Gain of MoRF binding (P = 0.0673);
MVP		0.85
MPC		0.58
ClinPred		0.90	D
GERP RS		4.7
Varity_R		0.28
gMVP		0.22

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

LitVar

Other links and lift over

dbSNP: rs576666131; hg19: chr11-82921439;