Genetic Variant NM_014862.4:c.28C>A (chr15-80404543-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014862.4(ARNT2):c.28C>A(p.Pro10Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P10S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ARNT2
NM_014862.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.74

Publications

0 publications found

Variant links:

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]

ARNT2 links:

ARNT2-DT (HGNC:56077): (ARNT2 divergent transcript)

ARNT2-DT links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17360693).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014862.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARNT2	NM_014862.4	MANE Select	c.28C>A	p.Pro10Thr	missense	Exon 1 of 19	NP_055677.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ARNT2	ENST00000303329.9	TSL:1 MANE Select	c.28C>A	p.Pro10Thr	missense	Exon 1 of 19	ENSP00000307479.4	Q9HBZ2-1
ARNT2	ENST00000529181.1	TSL:1	n.194C>A		non_coding_transcript_exon	Exon 1 of 5
ARNT2	ENST00000869656.1		c.28C>A	p.Pro10Thr	missense	Exon 1 of 20	ENSP00000539715.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1046216

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

511366

African (AFR)

AF:

0.00

AC:

AN:

20192

American (AMR)

AF:

0.00

AC:

AN:

16632

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13178

East Asian (EAS)

AF:

0.00

AC:

AN:

9582

South Asian (SAS)

AF:

0.00

AC:

AN:

51702

European-Finnish (FIN)

AF:

0.00

AC:

AN:

14752

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3036

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

879864

Other (OTH)

AF:

0.00

AC:

AN:

37278

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.56

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.14

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.30

FATHMM_MKL

Benign

0.54

LIST_S2

Benign

0.77

M_CAP

Pathogenic

0.64

MetaRNN

Benign

0.17

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.69

PhyloP100

1.7

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-0.040

REVEL

Benign

0.064

Sift

Benign

0.039

Sift4G

Uncertain

0.025

Polyphen

0.15

Vest4

0.21

MutPred

0.23

Gain of glycosylation at P10 (P = 0.0171)

MVP

0.27

MPC

1.7

ClinPred

0.43

GERP RS

1.8

PromoterAI

0.011

Neutral

(source)

Varity_R

0.076

gMVP

0.35

Mutation Taster

=86/14

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over