Variant 6-151468386-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_024573.3(ARMT1):c.602G>A(p.Gly201Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000012 in 1,582,512 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

ARMT1
NM_024573.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.70

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARMT1	NM_024573.3 linkuse as main transcript	c.602G>A	p.Gly201Glu	missense_variant	5/5	ENST00000367294.4	NP_078849.1	Q9H993
ARMT1	NM_001286562.2 linkuse as main transcript	c.245G>A	p.Gly82Glu	missense_variant	4/4		NP_001273491.1	Q9H993F5GZY1B4DPT6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ARMT1	ENST00000367294.4 linkuse as main transcript	c.602G>A	p.Gly201Glu	missense_variant	5/5	1	NM_024573.3	ENSP00000356263.3	Q9H993
ARMT1	ENST00000545879.5 linkuse as main transcript	c.245G>A	p.Gly82Glu	missense_variant	4/4	2		ENSP00000444121.1	F5GZY1
ARMT1	ENST00000494826.1 linkuse as main transcript	n.*325G>A		non_coding_transcript_exon_variant	4/4	2		ENSP00000435882.1	F2Z3I8
ARMT1	ENST00000494826.1 linkuse as main transcript	n.*325G>A		3_prime_UTR_variant	4/4	2		ENSP00000435882.1	F2Z3I8

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000889

AC:

AN:

225032

Hom.:

AF XY:

0.00000821

AC XY:

AN XY:

121840

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000188

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000112

AC:

AN:

1430354

Hom.:

Cov.:

AF XY:

0.0000113

AC XY:

AN XY:

710288

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000271

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000136

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152158

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000340

ExAC

AF:

0.00000824

AC:

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

Jan 03, 2024

The c.602G>A (p.G201E) alteration is located in exon 5 (coding exon 5) of the ARMT1 gene. This alteration results from a G to A substitution at nucleotide position 602, causing the glycine (G) at amino acid position 201 to be replaced by a glutamic acid (E). 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

Uncertain

0.55

BayesDel_addAF

Uncertain

0.029

BayesDel_noAF

Benign

-0.18

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.019

T;T

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.90

D;D

M_CAP

Benign

0.011

MetaRNN

Uncertain

0.63

D;D

MetaSVM

Benign

-1.1

PROVEAN

Pathogenic

-6.1

D;D

REVEL

Benign

0.27

Sift

Benign

0.067

T;D

Sift4G

Uncertain

0.0030

D;D

Polyphen

0.73

.;P

Vest4

0.52

MutPred

0.48

.;Gain of solvent accessibility (P = 0.012);

MVP

0.67

MPC

0.50

ClinPred

0.87

GERP RS

4.8

Varity_R

0.72

gMVP

0.51

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