9-21816529-A-G

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.121-185A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.494 in 152,030 control chromosomes in the GnomAD database, including 18,764 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.49 (18764 hom., cov: 31)
• Consequence: MTAP NM_002451.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.38

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=-0.97).
• BP6: Variant 9-21816529-A-G is Benign according to our data. Variant chr9-21816529-A-G is described in ClinVar as [Benign]. Clinvar id is 1285792.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.516 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTAP	NM_002451.4	c.121-185A>G		intron_variant		ENST00000644715.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTAP	ENST00000644715.2	c.121-185A>G		intron_variant			NM_002451.4	P1

Frequencies

GnomAD3 genomes AF: 0.494 AC: 75081 AN: 151912 Hom.: 18753 Cov.: 31

Gnomad AFR AF: 0.522

Gnomad AMI AF: 0.388

Gnomad AMR AF: 0.481

Gnomad ASJ AF: 0.491

Gnomad EAS AF: 0.465

Gnomad SAS AF: 0.291

Gnomad FIN AF: 0.457

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.505

Gnomad OTH AF: 0.483

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

GnomAD4 genome AF: 0.494 AC: 75147 AN: 152030 Hom.: 18764 Cov.: 31 AF XY: 0.487 AC XY: 36197 AN XY: 74306

Gnomad4 AFR AF: 0.521

Gnomad4 AMR AF: 0.481

Gnomad4 ASJ AF: 0.491

Gnomad4 EAS AF: 0.465

Gnomad4 SAS AF: 0.292

Gnomad4 FIN AF: 0.457

Gnomad4 NFE AF: 0.505

Gnomad4 OTH AF: 0.485

Alfa AF: 0.493 Hom.: 43117

Bravo AF: 0.503

Asia WGS AF: 0.391 AC: 1358 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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.13
Dann	Benign	0.33

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: rs7023329; hg19: chr9-21816528;