chr6-151468807-G-T

Position:

• chr6-151468807-G-T

Variant summary

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

The NM_024573.3(ARMT1):​c.1023G>T​(p.Glu341Asp) 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. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ARMT1 NM_024573.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0820

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]

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=0.13320854).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARMT1	NM_024573.3	c.1023G>T	p.Glu341Asp	missense_variant	5/5	ENST00000367294.4	NP_078849.1
ARMT1	NM_001286562.2	c.666G>T	p.Glu222Asp	missense_variant	4/4		NP_001273491.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARMT1	ENST00000367294.4	c.1023G>T	p.Glu341Asp	missense_variant	5/5	1	NM_024573.3	ENSP00000356263.3
ARMT1	ENST00000545879.5	c.666G>T	p.Glu222Asp	missense_variant	4/4	2		ENSP00000444121.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

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

Jan 24, 2024

The c.1023G>T (p.E341D) alteration is located in exon 5 (coding exon 5) of the ARMT1 gene. This alteration results from a G to T substitution at nucleotide position 1023, causing the glutamic acid (E) at amino acid position 341 to be replaced by an aspartic acid (D). 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	0.16
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	7.3
DANN	Benign	0.96
DEOGEN2	Benign	0.0021	T;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.93
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.76	T;T
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-0.94	T
PROVEAN	Benign	0.49	N;N
REVEL	Benign	0.063
Sift	Benign	0.57	T;T
Sift4G	Benign	0.79	T;T
Polyphen		0.0	.;B
Vest4		0.14
MutPred		0.52		.;Gain of helix (P = 0.132);
MVP		0.13
MPC		0.12
ClinPred		0.095	T
GERP RS		-2.6
Varity_R		0.18
gMVP		0.62

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: chr6-151789942;