NM_002451.4:c.121-185A>G

Variant names:

• chr9-21816529-A-G
• rs7023329
• NM_002451.4:c.121-185A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.38
• Publications: 84 publications found

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

ENSG00000264545 (HGNC:):

ACMG classification

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	c.121-185A>G		intron_variant	Intron 2 of 7	ENST00000644715.2	NP_002442.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTAP	ENST00000644715.2	c.121-185A>G		intron_variant	Intron 2 of 7		NM_002451.4	ENSP00000494373.1

Frequencies

GnomAD3 genomes AF: 0.494 AC: 75081 AN: 151912 Hom.: 18753 Cov.: 31

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.: 31 AF XY: 0.487 AC XY: 36197 AN XY: 74306

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

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

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
DANN	Benign	0.33
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7023329; hg19: chr9-21816528;