Variant 5-163518263-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_013283.5(MAT2B):c.905C>T(p.Thr302Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000769 in 1,613,928 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00095 ( 2 hom., cov: 33)

Exomes 𝑓: 0.00075 ( 13 hom. )

Consequence

MAT2B
NM_013283.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.870

Variant links:

Genes affected

MAT2B (HGNC:6905): (methionine adenosyltransferase 2 non-catalytic beta subunit) The protein encoded by this gene belongs to the methionine adenosyltransferase (MAT) family. MAT catalyzes the biosynthesis of S-adenosylmethionine from methionine and ATP. This protein is the regulatory beta subunit of MAT. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Nov 2012]

MAT2B links:

MAT2B (HGNC:):

MAT2B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005980402).

BP6

Variant 5-163518263-C-T is Benign according to our data. Variant chr5-163518263-C-T is described in ClinVar as [Benign]. Clinvar id is 717327.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000946 (144/152268) while in subpopulation EAS AF= 0.0212 (110/5180). AF 95% confidence interval is 0.018. There are 2 homozygotes in gnomad4. There are 58 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAT2B	NM_013283.5 linkuse as main transcript	c.905C>T	p.Thr302Ile	missense_variant	7/7	ENST00000321757.11	NP_037415.1	Q9NZL9-1A0A140VJP2
MAT2B	NM_182796.2 linkuse as main transcript	c.872C>T	p.Thr291Ile	missense_variant	7/7		NP_877725.1	Q9NZL9-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAT2B	ENST00000321757.11 linkuse as main transcript	c.905C>T	p.Thr302Ile	missense_variant	7/7	1	NM_013283.5	ENSP00000325425.6		Q9NZL9-1

Frequencies

GnomAD3 genomes

AF:

0.000946

AC:

144

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0212

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00188

AC:

472

AN:

251222

Hom.:

AF XY:

0.00172

AC XY:

234

AN XY:

135782

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0224

Gnomad SAS exome

AF:

0.00111

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000792

Gnomad OTH exome

AF:

0.00229

GnomAD4 exome

AF:

0.000751

AC:

1097

AN:

1461660

Hom.:

Cov.:

AF XY:

0.000755

AC XY:

549

AN XY:

727126

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0186

Gnomad4 SAS exome

AF:

0.00138

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000558

Gnomad4 OTH exome

AF:

0.00288

GnomAD4 genome

AF:

0.000946

AC:

144

AN:

152268

Hom.:

Cov.:

AF XY:

0.000779

AC XY:

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.000144

Gnomad4 AMR

AF:

0.000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0212

Gnomad4 SAS

AF:

0.00207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00143

Alfa

AF:

0.00127

Hom.:

Bravo

AF:

0.00132

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00176

AC:

214

Asia WGS

AF:

0.0200

AC:

AN:

3478

EpiCase

AF:

0.0000546

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.34

.;T

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.11

FATHMM_MKL

Benign

0.67

LIST_S2

Uncertain

0.90

D;D

MetaRNN

Benign

0.0060

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

.;L

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-1.7

N;N

REVEL

Benign

0.050

Sift

Benign

0.18

T;T

Sift4G

Benign

0.18

T;T

Polyphen

0.018

B;B

Vest4

0.16

MVP

0.45

MPC

0.42

ClinPred

0.017

GERP RS

3.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.19

gMVP

0.36

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