rs10757257

Variant names:

• chr9-21806565-G-A
• rs10757257
• NM_002451.4:c.33+3784G>A

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+3784G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 151,786 control chromosomes in the GnomAD database, including 9,747 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 0.34 (9747 hom., cov: 30)
• Consequence: MTAP NM_002451.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.280
• Publications: 29 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 (EAS) allele frequency at 95% confidence interval = 0.433 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTAP	NM_002451.4	c.33+3784G>A		intron_variant	Intron 1 of 7	ENST00000644715.2	NP_002442.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTAP	ENST00000644715.2	c.33+3784G>A		intron_variant	Intron 1 of 7		NM_002451.4	ENSP00000494373.1

Frequencies

GnomAD3 genomes AF: 0.341 AC: 51776 AN: 151668 Hom.: 9743 Cov.: 30

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.205

Gnomad AMR AF: 0.391

Gnomad ASJ AF: 0.370

Gnomad EAS AF: 0.447

Gnomad SAS AF: 0.267

Gnomad FIN AF: 0.415

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.416

Gnomad OTH AF: 0.336

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

GnomAD4 genome AF: 0.341 AC: 51806 AN: 151786 Hom.: 9747 Cov.: 30 AF XY: 0.341 AC XY: 25295 AN XY: 74166

African (AFR) AF: 0.178 AC: 7348 AN: 41396

American (AMR) AF: 0.391 AC: 5973 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.370 AC: 1281 AN: 3466

East Asian (EAS) AF: 0.448 AC: 2298 AN: 5132

South Asian (SAS) AF: 0.269 AC: 1293 AN: 4812

European-Finnish (FIN) AF: 0.415 AC: 4373 AN: 10540

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.416 AC: 28251 AN: 67858

Other (OTH) AF: 0.340 AC: 717 AN: 2106

Alfa AF: 0.389 Hom.: 10432

Bravo AF: 0.336

Asia WGS AF: 0.326 AC: 1131 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	4.5
DANN	Benign	0.63
PhyloP100		0.28
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: rs10757257; hg19: chr9-21806564;