rs10811629

Variant names:

• chr9-21840299-A-G
• rs10811629
• NM_002451.4:c.450+2289A>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.450+2289A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 152,078 control chromosomes in the GnomAD database, including 11,103 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 0.36 (11103 hom., cov: 32)
• Consequence: MTAP NM_002451.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.240
• Publications: 22 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTAP	NM_002451.4	c.450+2289A>G		intron_variant	Intron 5 of 7	ENST00000644715.2	NP_002442.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTAP	ENST00000644715.2	c.450+2289A>G		intron_variant	Intron 5 of 7		NM_002451.4	ENSP00000494373.1

Frequencies

GnomAD3 genomes AF: 0.365 AC: 55434 AN: 151960 Hom.: 11090 Cov.: 32

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.207

Gnomad AMR AF: 0.464

Gnomad ASJ AF: 0.380

Gnomad EAS AF: 0.445

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.425

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.436

Gnomad OTH AF: 0.361

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

GnomAD4 genome AF: 0.365 AC: 55476 AN: 152078 Hom.: 11103 Cov.: 32 AF XY: 0.366 AC XY: 27190 AN XY: 74340

African (AFR) AF: 0.198 AC: 8217 AN: 41504

American (AMR) AF: 0.465 AC: 7106 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.380 AC: 1321 AN: 3472

East Asian (EAS) AF: 0.446 AC: 2308 AN: 5176

South Asian (SAS) AF: 0.290 AC: 1402 AN: 4828

European-Finnish (FIN) AF: 0.425 AC: 4480 AN: 10532

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.435 AC: 29597 AN: 67962

Other (OTH) AF: 0.365 AC: 770 AN: 2112

Alfa AF: 0.411 Hom.: 56872

Bravo AF: 0.364

Asia WGS AF: 0.337 AC: 1172 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.0
DANN	Benign	0.69
PhyloP100		0.24
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: rs10811629; hg19: chr9-21840298;