Genetic Variant NM_002451.4:c.120+83_120+85dupAAA (chr9-21815590-T-TAAA) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_002451.4(MTAP):c.120+83_120+85dupAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.79 ( 45740 hom., cov: 0)

Exomes 𝑓: 0.46 ( 6803 hom. )

Failed GnomAD Quality Control

Consequence

MTAP
NM_002451.4 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.529

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

diaphyseal medullary stenosis-bone malignancy syndrome
Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: Genomics England PanelApp, G2P, Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen

MTAP links:

ENSG00000264545 (HGNC:):

ENSG00000264545 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 9-21815590-T-TAAA is Benign according to our data. Variant chr9-21815590-T-TAAA is described in ClinVar as [Benign]. Clinvar id is 1229885.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.851 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTAP	NM_002451.4 link	c.120+83_120+85dupAAA		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.120+83_120+85dupAAA		intron_variant	Intron 2 of 7		NM_002451.4	ENSP00000494373.1		Q13126-1

Frequencies

GnomAD3 genomes

AF:

0.786

AC:

114935

AN:

146210

Hom.:

45733

Cov.:

show subpopulations

Gnomad AFR

AF:

0.662

Gnomad AMI

AF:

0.636

Gnomad AMR

AF:

0.792

Gnomad ASJ

AF:

0.804

Gnomad EAS

AF:

0.725

Gnomad SAS

AF:

0.826

Gnomad FIN

AF:

0.823

Gnomad MID

AF:

0.765

Gnomad NFE

AF:

0.856

Gnomad OTH

AF:

0.797

GnomAD2 exomes

AF:

0.419

AC:

35861

AN:

85622

AF XY:

0.417

show subpopulations

Gnomad AFR exome

AF:

0.355

Gnomad AMR exome

AF:

0.392

Gnomad ASJ exome

AF:

0.405

Gnomad EAS exome

AF:

0.393

Gnomad FIN exome

AF:

0.461

Gnomad NFE exome

AF:

0.428

Gnomad OTH exome

AF:

0.422

GnomAD4 exome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.456

AC:

276824

AN:

606932

Hom.:

6803

Cov.:

AF XY:

0.456

AC XY:

147286

AN XY:

323116

show subpopulations

African (AFR)

AF:

0.389

AC:

5032

AN:

12952

American (AMR)

AF:

0.403

AC:

8040

AN:

19926

Ashkenazi Jewish (ASJ)

AF:

0.438

AC:

7526

AN:

17194

East Asian (EAS)

AF:

0.424

AC:

11584

AN:

27330

South Asian (SAS)

AF:

0.443

AC:

23353

AN:

52702

European-Finnish (FIN)

AF:

0.461

AC:

19955

AN:

43266

Middle Eastern (MID)

AF:

0.432

AC:

1024

AN:

2372

European-Non Finnish (NFE)

AF:

0.466

AC:

187180

AN:

401692

Other (OTH)

AF:

0.445

AC:

13130

AN:

29498

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

9864

19728

29591

39455

49319

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.786

AC:

114967

AN:

146270

Hom.:

45740

Cov.:

AF XY:

0.786

AC XY:

55711

AN XY:

70850

show subpopulations

African (AFR)

AF:

0.662

AC:

26295

AN:

39740

American (AMR)

AF:

0.792

AC:

11672

AN:

14740

Ashkenazi Jewish (ASJ)

AF:

0.804

AC:

2769

AN:

3446

East Asian (EAS)

AF:

0.725

AC:

3621

AN:

4994

South Asian (SAS)

AF:

0.826

AC:

3788

AN:

4588

European-Finnish (FIN)

AF:

0.823

AC:

7150

AN:

8684

Middle Eastern (MID)

AF:

0.773

AC:

218

AN:

282

European-Non Finnish (NFE)

AF:

0.856

AC:

57265

AN:

66868

Other (OTH)

AF:

0.798

AC:

1610

AN:

2018

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1060

2120

3180

4240

5300

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.413

Hom.:

233

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 20, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.53

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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NM_002451.4:c.120+83_120+85dupAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over