6-151464478-T-C

Position:

• chr6-151464478-T-C

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_024573.3(ARMT1):​c.418T>C​(p.Phe140Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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: 7.36

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 (HGNC:):

ACMG classification

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, 0.978

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARMT1	NM_024573.3	c.418T>C	p.Phe140Leu	missense_variant	4/5	ENST00000367294.4	NP_078849.1
ARMT1	NM_001286562.2	c.61T>C	p.Phe21Leu	missense_variant	3/4		NP_001273491.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARMT1	ENST00000367294.4	c.418T>C	p.Phe140Leu	missense_variant	4/5	1	NM_024573.3	ENSP00000356263.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

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

May 11, 2022

The c.418T>C (p.F140L) alteration is located in exon 4 (coding exon 4) of the ARMT1 gene. This alteration results from a T to C substitution at nucleotide position 418, causing the phenylalanine (F) at amino acid position 140 to be replaced by a leucine (L). 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	0.99
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.17
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.25	T;T
Eigen	Pathogenic	0.97
Eigen_PC	Pathogenic	0.89
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.90	D;D
M_CAP	Benign	0.055	D
MetaRNN	Pathogenic	0.98	D;D
MetaSVM	Benign	-0.46	T
PROVEAN	Pathogenic	-5.3	D;D
REVEL	Pathogenic	0.68
Sift	Pathogenic	0.0	D;D
Sift4G	Uncertain	0.015	D;D
Polyphen		1.0	.;D
Vest4		0.91
MutPred		0.93		.;Gain of ubiquitination at K144 (P = 0.068);
MVP		0.58
MPC		0.65
ClinPred		1.0	D
GERP RS		5.6
Varity_R		0.95
gMVP		0.78

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: chr6-151785613;