dbSNP rs7023329: MTAP:c.121-185A>G (chr9-21816529-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.121-185A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.494 in 152,030 control chromosomes in the GnomAD database, including 18,764 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.49 ( 18764 hom., cov: 31)

Consequence

MTAP
NM_002451.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.38

Publications

84 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=-0.97).

BP6

Variant 9-21816529-A-G is Benign according to our data. Variant chr9-21816529-A-G is described in ClinVar as [Benign]. Clinvar id is 1285792.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.516 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTAP	NM_002451.4 link	c.121-185A>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.121-185A>G		intron_variant	Intron 2 of 7		NM_002451.4	ENSP00000494373.1		Q13126-1

Frequencies

GnomAD3 genomes

AF:

0.494

AC:

75081

AN:

151912

Hom.:

18753

Cov.:

show subpopulations

Gnomad AFR

AF:

0.522

Gnomad AMI

AF:

0.388

Gnomad AMR

AF:

0.481

Gnomad ASJ

AF:

0.491

Gnomad EAS

AF:

0.465

Gnomad SAS

AF:

0.291

Gnomad FIN

AF:

0.457

Gnomad MID

AF:

0.443

Gnomad NFE

AF:

0.505

Gnomad OTH

AF:

0.483

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.494

AC:

75147

AN:

152030

Hom.:

18764

Cov.:

AF XY:

0.487

AC XY:

36197

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.521

AC:

21619

AN:

41458

American (AMR)

AF:

0.481

AC:

7350

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.491

AC:

1702

AN:

3468

East Asian (EAS)

AF:

0.465

AC:

2407

AN:

5174

South Asian (SAS)

AF:

0.292

AC:

1402

AN:

4808

European-Finnish (FIN)

AF:

0.457

AC:

4823

AN:

10554

Middle Eastern (MID)

AF:

0.469

AC:

138

AN:

294

European-Non Finnish (NFE)

AF:

0.505

AC:

34329

AN:

67966

Other (OTH)

AF:

0.485

AC:

1025

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1948

3896

5843

7791

9739

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.497

Hom.:

86270

Bravo

AF:

0.503

Asia WGS

AF:

0.391

AC:

1358

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

-0.97

CADD

Benign

0.13

(source)

DANN

Benign

0.33

PhyloP100

-1.4

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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rs7023329

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over