NM_002451.4:c.180-280A>G

Variant names:

• chr9-21817755-A-G
• rs7027989
• NM_002451.4:c.180-280A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002451.4(MTAP):​c.180-280A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.623 in 151,918 control chromosomes in the GnomAD database, including 30,711 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.62 (30711 hom., cov: 31)
• Consequence: MTAP NM_002451.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.656
• Publications: 12 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: ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, Genomics England PanelApp, Orphanet

ENSG00000264545 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 9-21817755-A-G is Benign according to our data. Variant chr9-21817755-A-G is described in ClinVar as Benign. ClinVar VariationId is 1221697.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.806 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002451.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTAP	NM_002451.4	MANE Select	c.180-280A>G		intron	N/A	NP_002442.2
	MTAP	NM_001396044.1		c.180-280A>G		intron	N/A	NP_001382973.1	Q13126-2
	MTAP	NM_001396041.1		c.180-280A>G		intron	N/A	NP_001382970.1	Q13126-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTAP	ENST00000644715.2	MANE Select	c.180-280A>G		intron	N/A	ENSP00000494373.1	Q13126-1
	MTAP	ENST00000580900.5	TSL:1	c.180-280A>G		intron	N/A	ENSP00000463424.1	Q13126-3
	MTAP	ENST00000580718.1	TSL:1	n.180-280A>G		intron	N/A	ENSP00000464616.1	J3QSB7

Frequencies

GnomAD3 genomes AF: 0.623 AC: 94538 AN: 151798 Hom.: 30657 Cov.: 31

Gnomad AFR AF: 0.813

Gnomad AMI AF: 0.536

Gnomad AMR AF: 0.613

Gnomad ASJ AF: 0.547

Gnomad EAS AF: 0.774

Gnomad SAS AF: 0.411

Gnomad FIN AF: 0.576

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.527

Gnomad OTH AF: 0.589

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

GnomAD4 genome AF: 0.623 AC: 94656 AN: 151918 Hom.: 30711 Cov.: 31 AF XY: 0.620 AC XY: 46039 AN XY: 74234

African (AFR) AF: 0.813 AC: 33750 AN: 41500

American (AMR) AF: 0.613 AC: 9362 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.547 AC: 1896 AN: 3468

East Asian (EAS) AF: 0.773 AC: 3936 AN: 5090

South Asian (SAS) AF: 0.412 AC: 1983 AN: 4814

European-Finnish (FIN) AF: 0.576 AC: 6075 AN: 10538

Middle Eastern (MID) AF: 0.531 AC: 156 AN: 294

European-Non Finnish (NFE) AF: 0.527 AC: 35761 AN: 67920

Other (OTH) AF: 0.591 AC: 1248 AN: 2112

Alfa AF: 0.569 Hom.: 14521

Bravo AF: 0.643

Asia WGS AF: 0.607 AC: 2108 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	5.4
DANN	Benign	0.36
PhyloP100		0.66
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: rs7027989; hg19: chr9-21817754;