9-21816574-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002451.4(MTAP):c.121-140G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.561 in 671,772 control chromosomes in the GnomAD database, including 108,827 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.63 (31474 hom., cov: 32)
  • Exomes 𝑓: 0.54 (77353 hom.)
• Consequence: MTAP NM_002451.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0550

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 9-21816574-G-A is Benign according to our data. Variant chr9-21816574-G-A is described in ClinVar as [Benign]. Clinvar id is 1230723.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.809 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTAP	NM_002451.4	c.121-140G>A		intron_variant		ENST00000644715.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTAP	ENST00000644715.2	c.121-140G>A		intron_variant			NM_002451.4	P1

Frequencies

GnomAD3 genomes AF: 0.632 AC: 96032 AN: 151884 Hom.: 31416 Cov.: 32

Gnomad AFR AF: 0.816

Gnomad AMI AF: 0.567

Gnomad AMR AF: 0.628

Gnomad ASJ AF: 0.581

Gnomad EAS AF: 0.708

Gnomad SAS AF: 0.415

Gnomad FIN AF: 0.544

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.550

Gnomad OTH AF: 0.604

GnomAD4 exome AF: 0.540 AC: 280577 AN: 519770 Hom.: 77353 AF XY: 0.530 AC XY: 145803 AN XY: 274892

Gnomad4 AFR exome AF: 0.809

Gnomad4 AMR exome AF: 0.647

Gnomad4 ASJ exome AF: 0.569

Gnomad4 EAS exome AF: 0.613

Gnomad4 SAS exome AF: 0.388

Gnomad4 FIN exome AF: 0.553

Gnomad4 NFE exome AF: 0.531

Gnomad4 OTH exome AF: 0.563

GnomAD4 genome AF: 0.633 AC: 96153 AN: 152002 Hom.: 31474 Cov.: 32 AF XY: 0.627 AC XY: 46620 AN XY: 74300

Gnomad4 AFR AF: 0.816

Gnomad4 AMR AF: 0.629

Gnomad4 ASJ AF: 0.581

Gnomad4 EAS AF: 0.708

Gnomad4 SAS AF: 0.416

Gnomad4 FIN AF: 0.544

Gnomad4 NFE AF: 0.549

Gnomad4 OTH AF: 0.605

Alfa AF: 0.584 Hom.: 6192

Bravo AF: 0.655

Asia WGS AF: 0.581 AC: 2021 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	2.4
Dann	Benign	0.53

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: rs7023680; hg19: chr9-21816573;