rs10114559

Positions:

• chr9-21816638-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002451.4(MTAP):​c.121-76T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.4 in 1,272,456 control chromosomes in the GnomAD database, including 106,373 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.36 (10828 hom., cov: 32)
  • Exomes 𝑓: 0.40 (95545 hom.)
• Consequence: MTAP NM_002451.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0880

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 9-21816638-T-C is Benign according to our data. Variant chr9-21816638-T-C is described in ClinVar as [Benign]. Clinvar id is 1258921.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.437 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTAP	NM_002451.4	c.121-76T>C		intron_variant		ENST00000644715.2	NP_002442.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTAP	ENST00000644715.2	c.121-76T>C		intron_variant			NM_002451.4	ENSP00000494373	P1

Frequencies

GnomAD3 genomes AF: 0.361 AC: 54824 AN: 151890 Hom.: 10823 Cov.: 32

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.415

Gnomad ASJ AF: 0.414

Gnomad EAS AF: 0.443

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.421

Gnomad MID AF: 0.338

Gnomad NFE AF: 0.441

Gnomad OTH AF: 0.364

GnomAD4 exome AF: 0.405 AC: 453757 AN: 1120448 Hom.: 95545 AF XY: 0.400 AC XY: 227793 AN XY: 570052

Gnomad4 AFR exome AF: 0.183

Gnomad4 AMR exome AF: 0.404

Gnomad4 ASJ exome AF: 0.398

Gnomad4 EAS exome AF: 0.399

Gnomad4 SAS exome AF: 0.234

Gnomad4 FIN exome AF: 0.431

Gnomad4 NFE exome AF: 0.428

Gnomad4 OTH exome AF: 0.388

GnomAD4 genome AF: 0.361 AC: 54868 AN: 152008 Hom.: 10828 Cov.: 32 AF XY: 0.360 AC XY: 26720 AN XY: 74296

Gnomad4 AFR AF: 0.196

Gnomad4 AMR AF: 0.415

Gnomad4 ASJ AF: 0.414

Gnomad4 EAS AF: 0.444

Gnomad4 SAS AF: 0.244

Gnomad4 FIN AF: 0.421

Gnomad4 NFE AF: 0.441

Gnomad4 OTH AF: 0.368

Alfa AF: 0.409 Hom.: 2896

Bravo AF: 0.357

Asia WGS AF: 0.318 AC: 1103 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.9
DANN	Benign	0.52

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: rs10114559; hg19: chr9-21816637; COSMIC: COSV66477123; COSMIC: COSV66477123;