rs745777019

Variant names:

• chr1-150813249-G-A
• rs745777019
• NM_001668.4:c.2203C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-150813249-G-A
• chr1-150813249-G-C

Variant summary

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

The NM_001668.4(ARNT):​c.2203C>T​(p.His735Tyr) variant causes a missense change. 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. H735D) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ARNT NM_001668.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.56

Genes affected

ARNT (HGNC:700): (aryl hydrocarbon receptor nuclear translocator) This gene encodes a protein containing a basic helix-loop-helix domain and two characteristic PAS domains along with a PAC domain. The encoded protein binds to ligand-bound aryl hydrocarbon receptor and aids in the movement of this complex to the nucleus, where it promotes the expression of genes involved in xenobiotic metabolism. This protein is also a co-factor for transcriptional regulation by hypoxia-inducible factor 1. Chromosomal translocation of this locus with the ETV6 (ets variant 6) gene on chromosome 12 have been described in leukemias. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2013]

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=0.31969965).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARNT	NM_001668.4	c.2203C>T	p.His735Tyr	missense_variant	Exon 21 of 22	ENST00000358595.10	NP_001659.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARNT	ENST00000358595.10	c.2203C>T	p.His735Tyr	missense_variant	Exon 21 of 22	1	NM_001668.4	ENSP00000351407.5
ARNT	ENST00000471844.6	n.*220C>T		non_coding_transcript_exon_variant	Exon 16 of 17	2		ENSP00000425899.1
ARNT	ENST00000471844.6	n.*220C>T		3_prime_UTR_variant	Exon 16 of 17	2		ENSP00000425899.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.055	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T;.;.;.
Eigen	Pathogenic	0.70
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.91	D;D;D;D
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.32	T;T;T;T
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.1	M;.;.;.
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.8	N;N;N;N
REVEL	Benign	0.19
Sift	Uncertain	0.0010	D;D;D;D
Sift4G	Uncertain	0.011	D;D;D;D
Polyphen		0.99	D;.;D;D
Vest4		0.42
MutPred		0.19		Gain of phosphorylation at H735 (P = 0.0313);.;.;.;
MVP		0.45
MPC		1.1
ClinPred		0.92	D
GERP RS		5.8
Varity_R		0.17
gMVP		0.24

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: rs745777019; hg19: chr1-150785725;