chr1-150858431-G-T

Position:

• chr1-150858431-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001668.4(ARNT):​c.55C>A​(p.Pro19Thr) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ARNT NM_001668.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.932

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1038619).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARNT	NM_001668.4	c.55C>A	p.Pro19Thr	missense_variant	2/22	ENST00000358595.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARNT	ENST00000358595.10	c.55C>A	p.Pro19Thr	missense_variant	2/22	1	NM_001668.4	P3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 19, 2022

The c.55C>A (p.P19T) alteration is located in exon 2 (coding exon 2) of the ARNT gene. This alteration results from a C to A substitution at nucleotide position 55, causing the proline (P) at amino acid position 19 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.10	T;.;.;.
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.52	D
LIST_S2	Uncertain	0.86	D;D;D;D
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.10	T;T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.89	L;L;.;L
MutationTaster	Benign	0.53	D;D;D;D
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.71	N;N;N;N
REVEL	Benign	0.089
Sift	Benign	0.14	T;T;T;T
Sift4G	Benign	1.0	T;T;T;T
Polyphen		0.0	B;.;B;B
Vest4		0.29
MutPred		0.15		Gain of glycosylation at P19 (P = 0.0482);Gain of glycosylation at P19 (P = 0.0482);.;Gain of glycosylation at P19 (P = 0.0482);
MVP		0.31
MPC		0.29
ClinPred		0.075	T
GERP RS		1.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.061
gMVP		0.26

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: chr1-150830907;