Genetic Variant SAMTOR:p.Arg25Trp (chr7-112939678-G-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_152556.3(SAMTOR):c.73C>T(p.Arg25Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000495 in 1,613,032 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: 𝑓 0.00030 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00052 ( 0 hom. )

Consequence

SAMTOR
NM_152556.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.74

Variant links:

Genes affected

SAMTOR (HGNC:26475): (base methyltransferase of 25S rRNA 2 homolog) Enables S-adenosyl-L-methionine binding activity. Involved in cellular response to amino acid starvation and negative regulation of TORC1 signaling. Colocalizes with GATOR1 complex and KICSTOR complex. [provided by Alliance of Genome Resources, Apr 2022]

SAMTOR links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07148638).

BS2

High AC in GnomAd4 at 45 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SAMTOR	NM_152556.3 link	c.73C>T	p.Arg25Trp	missense_variant	Exon 1 of 5	ENST00000297145.9	NP_689769.2	Q1RMZ1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMT2	ENST00000297145.9 link	c.73C>T	p.Arg25Trp	missense_variant	Exon 1 of 5	1	NM_152556.3	ENSP00000297145.4		Q1RMZ1
BMT2	ENST00000432572.1 link	c.-60C>T		upstream_gene_variant		5		ENSP00000408654.1		H0Y6Y0

Frequencies

GnomAD3 genomes

AF:

0.000296

AC:

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

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:

0.000456

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000325

AC:

AN:

246366

Hom.:

AF XY:

0.000335

AC XY:

AN XY:

134228

show subpopulations

Gnomad AFR exome

AF:

0.000130

Gnomad AMR exome

AF:

0.000435

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.000142

Gnomad NFE exome

AF:

0.000514

Gnomad OTH exome

AF:

0.000333

GnomAD4 exome

AF:

0.000515

AC:

753

AN:

1460736

Hom.:

Cov.:

AF XY:

0.000484

AC XY:

352

AN XY:

726680

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.000470

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.0000572

Gnomad4 NFE exome

AF:

0.000636

Gnomad4 OTH exome

AF:

0.000265

GnomAD4 genome

AF:

0.000295

AC:

AN:

152296

Hom.:

Cov.:

AF XY:

0.000349

AC XY:

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.000192

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000456

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000578

Hom.:

Bravo

AF:

0.000446

ESP6500AA

AF:

0.000266

AC:

ESP6500EA

AF:

0.00122

AC:

ExAC

AF:

0.000273

AC:

EpiCase

AF:

0.000491

EpiControl

AF:

0.000356

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 17, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.73C>T (p.R25W) alteration is located in exon 1 (coding exon 1) of the BMT2 gene. This alteration results from a C to T substitution at nucleotide position 73, causing the arginine (R) at amino acid position 25 to be replaced by a tryptophan (W). 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

0.12

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.22

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.019

Eigen

Benign

0.024

Eigen_PC

Benign

0.084

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.81

M_CAP

Pathogenic

0.30

MetaRNN

Benign

0.071

MetaSVM

Benign

-1.1

PROVEAN

Benign

-0.56

REVEL

Benign

0.28

Sift

Uncertain

0.0060

Sift4G

Uncertain

0.025

Polyphen

0.99

Vest4

0.26

MVP

0.043

MPC

1.5

ClinPred

0.083

GERP RS

3.1

Varity_R

0.22

gMVP

0.27

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