Genetic Variant MTAP:c.121-140G>A (chr9-21816574-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002451.4(MTAP):c.121-140G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.561 in 671,772 control chromosomes in the GnomAD database, including 108,827 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.63 ( 31474 hom., cov: 32)

Exomes 𝑓: 0.54 ( 77353 hom. )

Consequence

MTAP
NM_002451.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0550

Variant links:

Genes affected

MTAP (HGNC:7413): (methylthioadenosine phosphorylase) This gene encodes an enzyme that plays a major role in polyamine metabolism and is important for the salvage pathway of both adenine and methionine. The encoded enzyme is deficient in many cancers. Multiple alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Sep 2021]

MTAP links:

ENSG00000264545 (HGNC:):

ENSG00000264545 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 9-21816574-G-A is Benign according to our data. Variant chr9-21816574-G-A is described in ClinVar as [Benign]. Clinvar id is 1230723.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.809 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTAP	NM_002451.4 link	c.121-140G>A		intron_variant	Intron 2 of 7	ENST00000644715.2	NP_002442.2	Q13126-1A0A384ME80

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTAP	ENST00000644715.2 link	c.121-140G>A		intron_variant	Intron 2 of 7		NM_002451.4	ENSP00000494373.1		Q13126-1

Frequencies

GnomAD3 genomes

AF:

0.632

AC:

96032

AN:

151884

Hom.:

31416

Cov.:

show subpopulations

Gnomad AFR

AF:

0.816

Gnomad AMI

AF:

0.567

Gnomad AMR

AF:

0.628

Gnomad ASJ

AF:

0.581

Gnomad EAS

AF:

0.708

Gnomad SAS

AF:

0.415

Gnomad FIN

AF:

0.544

Gnomad MID

AF:

0.576

Gnomad NFE

AF:

0.550

Gnomad OTH

AF:

0.604

GnomAD4 exome

AF:

0.540

AC:

280577

AN:

519770

Hom.:

77353

AF XY:

0.530

AC XY:

145803

AN XY:

274892

show subpopulations

African (AFR)

AF:

0.809

AC:

10351

AN:

12798

American (AMR)

AF:

0.647

AC:

13440

AN:

20774

Ashkenazi Jewish (ASJ)

AF:

0.569

AC:

8019

AN:

14082

East Asian (EAS)

AF:

0.613

AC:

19166

AN:

31288

South Asian (SAS)

AF:

0.388

AC:

16030

AN:

41360

European-Finnish (FIN)

AF:

0.553

AC:

18728

AN:

33886

Middle Eastern (MID)

AF:

0.524

AC:

1500

AN:

2862

European-Non Finnish (NFE)

AF:

0.531

AC:

177537

AN:

334638

Other (OTH)

AF:

0.563

AC:

15806

AN:

28082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

5442

10883

16325

21766

27208

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.633

AC:

96153

AN:

152002

Hom.:

31474

Cov.:

AF XY:

0.627

AC XY:

46620

AN XY:

74300

show subpopulations

African (AFR)

AF:

0.816

AC:

33837

AN:

41468

American (AMR)

AF:

0.629

AC:

9606

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.581

AC:

2016

AN:

3472

East Asian (EAS)

AF:

0.708

AC:

3662

AN:

5170

South Asian (SAS)

AF:

0.416

AC:

2002

AN:

4810

European-Finnish (FIN)

AF:

0.544

AC:

5734

AN:

10544

Middle Eastern (MID)

AF:

0.589

AC:

172

AN:

292

European-Non Finnish (NFE)

AF:

0.549

AC:

37329

AN:

67940

Other (OTH)

AF:

0.605

AC:

1279

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1721

3442

5164

6885

8606

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.574

Hom.:

11104

Bravo

AF:

0.655

Asia WGS

AF:

0.581

AC:

2021

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

2.4

(source)

DANN

Benign

0.53

PhyloP100

-0.055

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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9-21816574-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over