rs10811629

Positions:

• chr9-21840299-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ENSG00000264545 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
MTAP	NM_002451.4	c.450+2289A>G		intron_variant		ENST00000644715.2	NP_002442.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTAP	ENST00000644715.2	c.450+2289A>G		intron_variant			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

Gnomad4 AFR AF: 0.198

Gnomad4 AMR AF: 0.465

Gnomad4 ASJ AF: 0.380

Gnomad4 EAS AF: 0.446

Gnomad4 SAS AF: 0.290

Gnomad4 FIN AF: 0.425

Gnomad4 NFE AF: 0.435

Gnomad4 OTH AF: 0.365

Alfa AF: 0.414 Hom.: 27413

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs10811629; hg19: chr9-21840298;