Genetic Variant NM_013283.5:c.259-270A>G (chr5-163513285-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_013283.5(MAT2B):c.259-270A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0339 in 295,730 control chromosomes in the GnomAD database, including 231 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.031 ( 102 hom., cov: 33)

Exomes 𝑓: 0.037 ( 129 hom. )

Consequence

MAT2B
NM_013283.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.454

Publications

2 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0645 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAT2B	NM_013283.5 link	c.259-270A>G		intron_variant	Intron 2 of 6	ENST00000321757.11	NP_037415.1	Q9NZL9-1A0A140VJP2
MAT2B	NM_182796.2 link	c.226-270A>G		intron_variant	Intron 2 of 6		NP_877725.1	Q9NZL9-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAT2B	ENST00000321757.11 link	c.259-270A>G		intron_variant	Intron 2 of 6	1	NM_013283.5	ENSP00000325425.6		Q9NZL9-1

Frequencies

GnomAD3 genomes

AF:

0.0309

AC:

4702

AN:

152200

Hom.:

102

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00837

Gnomad AMI

AF:

0.0998

Gnomad AMR

AF:

0.0352

Gnomad ASJ

AF:

0.0233

Gnomad EAS

AF:

0.0701

Gnomad SAS

AF:

0.0199

Gnomad FIN

AF:

0.0458

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0385

Gnomad OTH

AF:

0.0325

GnomAD4 exome

AF:

0.0371

AC:

5314

AN:

143412

Hom.:

129

Cov.:

AF XY:

0.0356

AC XY:

2701

AN XY:

75768

show subpopulations

African (AFR)

AF:

0.00847

AC:

AN:

4488

American (AMR)

AF:

0.0513

AC:

327

AN:

6370

Ashkenazi Jewish (ASJ)

AF:

0.0224

AC:

100

AN:

4456

East Asian (EAS)

AF:

0.0846

AC:

802

AN:

9476

South Asian (SAS)

AF:

0.0189

AC:

281

AN:

14830

European-Finnish (FIN)

AF:

0.0432

AC:

265

AN:

6132

Middle Eastern (MID)

AF:

0.0308

AC:

AN:

584

European-Non Finnish (NFE)

AF:

0.0364

AC:

3235

AN:

88784

Other (OTH)

AF:

0.0299

AC:

248

AN:

8292

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

246

493

739

986

1232

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

160

200

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0309

AC:

4706

AN:

152318

Hom.:

102

Cov.:

AF XY:

0.0313

AC XY:

2335

AN XY:

74492

show subpopulations

African (AFR)

AF:

0.00835

AC:

347

AN:

41566

American (AMR)

AF:

0.0350

AC:

535

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0233

AC:

AN:

3470

East Asian (EAS)

AF:

0.0705

AC:

366

AN:

5194

South Asian (SAS)

AF:

0.0201

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.0458

AC:

487

AN:

10624

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0385

AC:

2619

AN:

68016

Other (OTH)

AF:

0.0350

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

227

455

682

910

1137

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

180

240

300

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0364

Hom.:

Bravo

AF:

0.0318

Asia WGS

AF:

0.0680

AC:

236

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

7.3

(source)

DANN

Benign

0.38

PhyloP100

0.45

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over