Variant 6-151468377-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_024573.3(ARMT1):c.593T>C(p.Leu198Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0000014 in 1,425,260 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ARMT1
NM_024573.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.20

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 Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.955

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARMT1	NM_024573.3 linkuse as main transcript	c.593T>C	p.Leu198Pro	missense_variant	5/5	ENST00000367294.4	NP_078849.1	Q9H993
ARMT1	NM_001286562.2 linkuse as main transcript	c.236T>C	p.Leu79Pro	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.593T>C	p.Leu198Pro	missense_variant	5/5	1	NM_024573.3	ENSP00000356263.3	Q9H993
ARMT1	ENST00000545879.5 linkuse as main transcript	c.236T>C	p.Leu79Pro	missense_variant	4/4	2		ENSP00000444121.1	F5GZY1
ARMT1	ENST00000494826.1 linkuse as main transcript	n.*316T>C		non_coding_transcript_exon_variant	4/4	2		ENSP00000435882.1	F2Z3I8
ARMT1	ENST00000494826.1 linkuse as main transcript	n.*316T>C		3_prime_UTR_variant	4/4	2		ENSP00000435882.1	F2Z3I8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000140

AC:

AN:

1425260

Hom.:

Cov.:

AF XY:

0.00000283

AC XY:

AN XY:

707266

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000125

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.11e-7

Gnomad4 OTH exome

AF:

0.00

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 05, 2024

The c.593T>C (p.L198P) alteration is located in exon 5 (coding exon 5) of the ARMT1 gene. This alteration results from a T to C substitution at nucleotide position 593, causing the leucine (L) at amino acid position 198 to be replaced by a proline (P). 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

Pathogenic

0.74

BayesDel_addAF

Uncertain

0.058

BayesDel_noAF

Benign

-0.15

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

T;T

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.84

T;T

M_CAP

Benign

0.019

MetaRNN

Pathogenic

0.96

D;D

MetaSVM

Benign

-0.95

PROVEAN

Pathogenic

-5.4

D;D

REVEL

Uncertain

0.33

Sift

Uncertain

0.0030

D;D

Sift4G

Uncertain

0.0040

D;D

Polyphen

1.0

.;D

Vest4

0.63

MutPred

0.88

.;Gain of disorder (P = 0.0326);

MVP

0.70

MPC

0.75

ClinPred

0.98

GERP RS

4.5

Varity_R

0.83

gMVP

0.74

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over