dbSNP rs7023474: MTAP:c.121-67A>G (chr9-21816647-A-G) – 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.121-67A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.556 in 1,408,308 control chromosomes in the GnomAD database, including 223,780 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.63 ( 31459 hom., cov: 32)

Exomes 𝑓: 0.55 ( 192321 hom. )

Consequence

MTAP
NM_002451.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.622

Publications

6 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 9-21816647-A-G is Benign according to our data. Variant chr9-21816647-A-G is described in ClinVar as [Benign]. Clinvar id is 1239449.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.121-67A>G		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.121-67A>G		intron_variant	Intron 2 of 7		NM_002451.4	ENSP00000494373.1		Q13126-1

Frequencies

GnomAD3 genomes

AF:

0.632

AC:

96005

AN:

151874

Hom.:

31401

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:

0.414

Gnomad FIN

AF:

0.543

Gnomad MID

AF:

0.576

Gnomad NFE

AF:

0.549

Gnomad OTH

AF:

0.603

GnomAD4 exome

AF:

0.547

AC:

687281

AN:

1256316

Hom.:

192321

AF XY:

0.540

AC XY:

342013

AN XY:

632976

show subpopulations

African (AFR)

AF:

0.821

AC:

23725

AN:

28912

American (AMR)

AF:

0.665

AC:

26406

AN:

39728

Ashkenazi Jewish (ASJ)

AF:

0.571

AC:

13639

AN:

23886

East Asian (EAS)

AF:

0.636

AC:

24254

AN:

38150

South Asian (SAS)

AF:

0.405

AC:

31281

AN:

77154

European-Finnish (FIN)

AF:

0.560

AC:

27080

AN:

48350

Middle Eastern (MID)

AF:

0.527

AC:

2770

AN:

5258

European-Non Finnish (NFE)

AF:

0.540

AC:

508018

AN:

941520

Other (OTH)

AF:

0.564

AC:

30108

AN:

53358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

13602

27203

40805

54406

68008

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.632

AC:

96126

AN:

151992

Hom.:

31459

Cov.:

AF XY:

0.627

AC XY:

46581

AN XY:

74272

show subpopulations

African (AFR)

AF:

0.816

AC:

33853

AN:

41490

American (AMR)

AF:

0.628

AC:

9598

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.581

AC:

2016

AN:

3472

East Asian (EAS)

AF:

0.708

AC:

3658

AN:

5164

South Asian (SAS)

AF:

0.416

AC:

1999

AN:

4810

European-Finnish (FIN)

AF:

0.543

AC:

5724

AN:

10538

Middle Eastern (MID)

AF:

0.588

AC:

173

AN:

294

European-Non Finnish (NFE)

AF:

0.549

AC:

37314

AN:

67928

Other (OTH)

AF:

0.604

AC:

1275

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1744

3487

5231

6974

8718

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.583

Hom.:

4705

Bravo

AF:

0.655

Asia WGS

AF:

0.581

AC:

2020

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

Jun 19, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

6.3

(source)

DANN

Benign

0.77

PhyloP100

0.62

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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rs7023474

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