rs375524509

Variant names:

• chr15-80450972-C-G
• NM_014862.4:c.124C>G

Your query was ambiguous. Multiple possible variants found:

• chr15-80450972-C-G
• chr15-80450972-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1 PM2 BP4

The NM_014862.4(ARNT2):​c.124C>G​(p.Arg42Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,670 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: 6.8e-7 (0 hom.)
• Consequence: ARNT2 NM_014862.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.95

Genes affected

ARNT2 (HGNC:16876): (aryl hydrocarbon receptor nuclear translocator 2) This gene encodes a member of the basic-helix-loop-helix-Per-Arnt-Sim (bHLH-PAS) superfamily of transcription factors. The encoded protein acts as a partner for several sensor proteins of the bHLH-PAS family, forming heterodimers with the sensor proteins that bind regulatory DNA sequences in genes responsive to developmental and environmental stimuli. Under hypoxic conditions, the encoded protein complexes with hypoxia-inducible factor 1alpha in the nucleus and this complex binds to hypoxia-responsive elements in enhancers and promoters of oxygen-responsive genes. A highly similar protein in mouse forms functional complexes with both aryl hydrocarbon receptors and Single-minded proteins, suggesting additional roles for the encoded protein in the metabolism of xenobiotic compounds and the regulation of neurogenesis, respectively. [provided by RefSeq, Dec 2013]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM1: In a modified_residue Omega-N-methylarginine (size 0) in uniprot entity ARNT2_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26818097).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARNT2	NM_014862.4	c.124C>G	p.Arg42Gly	missense_variant	Exon 2 of 19	ENST00000303329.9	NP_055677.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARNT2	ENST00000303329.9	c.124C>G	p.Arg42Gly	missense_variant	Exon 2 of 19	1	NM_014862.4	ENSP00000307479.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461670 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727138

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.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
BayesDel_addAF	Benign	-0.0029	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.26	T;.;.;.
Eigen	Benign	-0.10
Eigen_PC	Benign	0.044
FATHMM_MKL	Benign	0.68	D
LIST_S2	Uncertain	0.95	D;D;.;D
M_CAP	Benign	0.0081	T
MetaRNN	Benign	0.27	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M;.;.;.
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-1.4	N;.;N;N
REVEL	Benign	0.12
Sift	Uncertain	0.0040	D;.;D;D
Sift4G	Benign	0.080	T;T;T;T
Polyphen		0.025	B;.;.;.
Vest4		0.48
MutPred		0.37		Loss of MoRF binding (P = 0.021);Loss of MoRF binding (P = 0.021);.;.;
MVP		0.76
MPC		1.4
ClinPred		0.79	D
GERP RS		3.9
Varity_R		0.18
gMVP		0.67

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: chr15-80743313;