Variant 6-151458439-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001286562.2(ARMT1):c.-99A>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000685 in 1,459,540 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 (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000069 ( 0 hom. )

Consequence

ARMT1
NM_001286562.2 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.00600

Variant links:

Genes affected

ARMT1 (HGNC:17872): (acidic residue methyltransferase 1) Enables S-adenosylmethionine-dependent methyltransferase activity; enzyme binding activity; and protein carboxyl O-methyltransferase activity. Involved in methylation and regulation of response to DNA damage stimulus. [provided by Alliance of Genome Resources, Apr 2022]

ARMT1 links:

ARMT1 (HGNC:):

ARMT1 links:

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ACMG classification

Classification made for transcript

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=0.10089052).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARMT1	NM_024573.3 linkuse as main transcript	c.259A>G	p.Ile87Val	missense_variant	3/5	ENST00000367294.4	NP_078849.1	Q9H993
ARMT1	NM_001286562.2 linkuse as main transcript	c.-99A>G		5_prime_UTR_premature_start_codon_gain_variant	2/4		NP_001273491.1	Q9H993F5GZY1B4DPT6
ARMT1	NM_001286562.2 linkuse as main transcript	c.-99A>G		5_prime_UTR_variant	2/4		NP_001273491.1	Q9H993F5GZY1B4DPT6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARMT1	ENST00000367294.4 linkuse as main transcript	c.259A>G	p.Ile87Val	missense_variant	3/5	1	NM_024573.3	ENSP00000356263.3		Q9H993

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251342

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135864

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000685

AC:

AN:

1459540

Hom.:

Cov.:

AF XY:

0.00000689

AC XY:

AN XY:

726204

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000721

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 28, 2023

The c.259A>G (p.I87V) alteration is located in exon 3 (coding exon 3) of the ARMT1 gene. This alteration results from a A to G substitution at nucleotide position 259, causing the isoleucine (I) at amino acid position 87 to be replaced by a valine (V). 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

0.067

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.71

CADD

Benign

8.7

DANN

Benign

0.83

DEOGEN2

Benign

0.0046

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.59

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.58

M_CAP

Benign

0.0022

MetaRNN

Benign

0.10

MetaSVM

Benign

-0.95

PROVEAN

Benign

-0.14

REVEL

Benign

0.024

Sift

Benign

0.21

Sift4G

Benign

0.69

Polyphen

0.0030

Vest4

0.17

MutPred

0.45

Loss of catalytic residue at L92 (P = 0.0617);

MVP

0.15

MPC

0.11

ClinPred

0.052

GERP RS

1.9

Varity_R

0.032

gMVP

0.16

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over