9-21804618-A-G

Variant names:

• chr9-21804618-A-G
• rs869330
• NM_002451.4:c.33+1837A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002451.4(MTAP):​c.33+1837A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.612 in 152,086 control chromosomes in the GnomAD database, including 29,950 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.61 (29950 hom., cov: 32)
• Consequence: MTAP NM_002451.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.395
• Publications: 7 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.818 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTAP	NM_002451.4	MANE Select	c.33+1837A>G		intron	N/A	NP_002442.2
	MTAP	NM_001396044.1		c.33+1837A>G		intron	N/A	NP_001382973.1
	MTAP	NM_001396041.1		c.33+1837A>G		intron	N/A	NP_001382970.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTAP	ENST00000644715.2	MANE Select	c.33+1837A>G		intron	N/A	ENSP00000494373.1
	MTAP	ENST00000580900.5	TSL:1	c.33+1837A>G		intron	N/A	ENSP00000463424.1
	MTAP	ENST00000580718.1	TSL:1	n.33+1837A>G		intron	N/A	ENSP00000464616.1

Frequencies

GnomAD3 genomes AF: 0.612 AC: 92949 AN: 151966 Hom.: 29888 Cov.: 32

Gnomad AFR AF: 0.825

Gnomad AMI AF: 0.409

Gnomad AMR AF: 0.600

Gnomad ASJ AF: 0.530

Gnomad EAS AF: 0.708

Gnomad SAS AF: 0.379

Gnomad FIN AF: 0.512

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.518

Gnomad OTH AF: 0.580

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

GnomAD4 genome AF: 0.612 AC: 93082 AN: 152086 Hom.: 29950 Cov.: 32 AF XY: 0.607 AC XY: 45089 AN XY: 74334

African (AFR) AF: 0.825 AC: 34218 AN: 41476

American (AMR) AF: 0.601 AC: 9184 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.530 AC: 1839 AN: 3470

East Asian (EAS) AF: 0.709 AC: 3657 AN: 5160

South Asian (SAS) AF: 0.382 AC: 1839 AN: 4820

European-Finnish (FIN) AF: 0.512 AC: 5419 AN: 10574

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.518 AC: 35186 AN: 67986

Other (OTH) AF: 0.581 AC: 1223 AN: 2104

Alfa AF: 0.598 Hom.: 4339

Bravo AF: 0.637

Asia WGS AF: 0.557 AC: 1937 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.7
DANN	Benign	0.38
PhyloP100		0.40
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs869330; hg19: chr9-21804617;