Genetic Variant ARNT2:p.Thr3Asn (chr15-80404523-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_014862.4(ARNT2):c.8C>A(p.Thr3Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,076,030 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T3A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

ARNT2
NM_014862.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.73

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: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.20640177).

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.8C>A	p.Thr3Asn	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.8C>A	p.Thr3Asn	missense	Exon 1 of 19	ENSP00000307479.4	Q9HBZ2-1
ARNT2	ENST00000529181.1	TSL:1	n.174C>A		non_coding_transcript_exon	Exon 1 of 5
ARNT2	ENST00000869656.1		c.8C>A	p.Thr3Asn	missense	Exon 1 of 20	ENSP00000539715.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000149

AC:

AN:

1076030

Hom.:

Cov.:

AF XY:

0.00000946

AC XY:

AN XY:

528492

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

20670

American (AMR)

AF:

0.00

AC:

AN:

17810

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14248

East Asian (EAS)

AF:

0.00

AC:

AN:

10602

South Asian (SAS)

AF:

0.00

AC:

AN:

56620

European-Finnish (FIN)

AF:

0.00

AC:

AN:

16702

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3266

European-Non Finnish (NFE)

AF:

0.0000178

AC:

AN:

897434

Other (OTH)

AF:

0.00

AC:

AN:

38678

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.49

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Uncertain

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.14

Eigen

Benign

-0.14

Eigen_PC

Benign

-0.094

FATHMM_MKL

Benign

0.63

LIST_S2

Benign

0.84

M_CAP

Pathogenic

0.40

MetaRNN

Benign

0.21

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

PhyloP100

1.7

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-0.34

REVEL

Benign

0.057

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.024

Polyphen

0.53

Vest4

0.23

MutPred

0.11

Loss of glycosylation at T3 (P = 0.0021)

MVP

0.19

MPC

1.5

ClinPred

0.64

GERP RS

2.7

PromoterAI

-0.14

Neutral

(source)

Varity_R

0.18

gMVP

0.33

Mutation Taster

=79/21

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over