NM_001300975.2:c.373C>G

Variant names:

• chr11-83210342-C-G
• rs764888146
• NM_001300975.2:c.373C>G

Variant summary

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

The NM_001300975.2(ANKRD42):​c.373C>G​(p.Arg125Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,612 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ANKRD42 NM_001300975.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.294

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=0.39387208).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD42	NM_001300975.2	c.373C>G	p.Arg125Gly	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.373C>G	p.Arg125Gly	missense_variant	Exon 4 of 11	1	NM_001300975.2	ENSP00000435790.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461612 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727114

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.064	.;.;.;.;.;T;.
Eigen	Uncertain	0.22
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Benign	0.69	D
LIST_S2	Uncertain	0.86	D;D;D;D;T;D;D
M_CAP	Benign	0.058	D
MetaRNN	Benign	0.39	T;T;T;T;T;T;T
MetaSVM	Uncertain	-0.17	T
MutationAssessor	Benign	0.55	.;.;.;.;.;N;.
PrimateAI	Benign	0.44	T
PROVEAN	Pathogenic	-4.4	D;D;D;D;D;D;D
REVEL	Benign	0.20
Sift	Uncertain	0.013	D;T;D;T;D;D;D
Sift4G	Benign	0.30	T;T;T;T;T;T;T
Polyphen		1.0	D;.;.;.;.;D;D
Vest4		0.49
MutPred		0.45		Gain of catalytic residue at C127 (P = 0.0896);.;Gain of catalytic residue at C127 (P = 0.0896);Gain of catalytic residue at C127 (P = 0.0896);Gain of catalytic residue at C127 (P = 0.0896);.;Gain of catalytic residue at C127 (P = 0.0896);
MVP		0.84
MPC		0.58
ClinPred		0.96	D
GERP RS		5.0
Varity_R		0.38
gMVP		0.27

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: rs764888146; hg19: chr11-82921384;