11-83198515-A-T

Variant names:

• chr11-83198515-A-T
• rs1861747680
• ENST00000528722:c.-245A>T

Variant summary

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

The ENST00000528722(ANKRD42):​c.-245A>T variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.000000684 in 1,461,622 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: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ANKRD42 ENST00000528722 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.88

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

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.95A>T	p.Asp32Val	missense_variant	Exon 2 of 11	ENST00000533342.6	NP_001287904.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKRD42	ENST00000533342.6	c.95A>T	p.Asp32Val	missense_variant	Exon 2 of 11	1	NM_001300975.2	ENSP00000435790.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461622 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727122

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Uncertain	0.090	D
BayesDel_noAF	Benign	-0.11
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.028	.;.;.;.;T;.
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.92	D;D;D;D;D;D
M_CAP	Benign	0.039	D
MetaRNN	Uncertain	0.63	D;D;D;D;D;D
MetaSVM	Benign	-0.75	T
MutationAssessor	Benign	0.29	N;.;.;.;N;.
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-4.4	D;D;D;D;D;D
REVEL	Benign	0.28
Sift	Benign	0.33	T;D;T;D;T;D
Sift4G	Benign	0.57	T;T;T;T;T;T
Polyphen		0.96	D;.;.;.;D;P
Vest4		0.63
MutPred		0.76		Loss of catalytic residue at D32 (P = 0.0118);Loss of catalytic residue at D32 (P = 0.0118);Loss of catalytic residue at D32 (P = 0.0118);Loss of catalytic residue at D32 (P = 0.0118);Loss of catalytic residue at D32 (P = 0.0118);Loss of catalytic residue at D32 (P = 0.0118);
MVP		0.73
MPC		0.58
ClinPred		0.94	D
GERP RS		4.6
Varity_R		0.46
gMVP		0.43

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

LitVar

Other links and lift over

dbSNP: rs1861747680; hg19: chr11-82909557;