9-21832743-A-G

Variant names:

• chr9-21832743-A-G
• rs7874112
• NM_002451.4:c.348-5165A>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.348-5165A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 152,052 control chromosomes in the GnomAD database, including 5,850 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 0.23 (5850 hom., cov: 32)
• Consequence: MTAP NM_002451.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.823
• Publications: 4 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.467 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.348-5165A>G		intron	N/A	NP_002442.2
	MTAP	NM_001396044.1		c.348-5165A>G		intron	N/A	NP_001382973.1	Q13126-2
	MTAP	NM_001396041.1		c.348-5165A>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.348-5165A>G		intron	N/A	ENSP00000494373.1	Q13126-1
	MTAP	ENST00000580900.5	TSL:1	c.348-5165A>G		intron	N/A	ENSP00000463424.1	Q13126-3
	MTAP	ENST00000580718.1	TSL:1	n.348-5165A>G		intron	N/A	ENSP00000464616.1	J3QSB7

Frequencies

GnomAD3 genomes AF: 0.231 AC: 35044 AN: 151934 Hom.: 5847 Cov.: 32

Gnomad AFR AF: 0.473

Gnomad AMI AF: 0.331

Gnomad AMR AF: 0.195

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.262

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.125

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.209

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

GnomAD4 genome AF: 0.231 AC: 35059 AN: 152052 Hom.: 5850 Cov.: 32 AF XY: 0.227 AC XY: 16858 AN XY: 74344

African (AFR) AF: 0.472 AC: 19569 AN: 41426

American (AMR) AF: 0.195 AC: 2978 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.159 AC: 553 AN: 3470

East Asian (EAS) AF: 0.262 AC: 1354 AN: 5172

South Asian (SAS) AF: 0.163 AC: 787 AN: 4820

European-Finnish (FIN) AF: 0.125 AC: 1318 AN: 10584

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.113 AC: 7702 AN: 67986

Other (OTH) AF: 0.206 AC: 436 AN: 2112

Alfa AF: 0.152 Hom.: 1853

Bravo AF: 0.251

Asia WGS AF: 0.236 AC: 819 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.4
DANN	Benign	0.49
PhyloP100		0.82
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: rs7874112; hg19: chr9-21832742;