9-21817755-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.180-280A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.623 in 151,918 control chromosomes in the GnomAD database, including 30,711 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.62 (30711 hom., cov: 31)
• Consequence: MTAP NM_002451.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.656

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=-0.98).
• BP6: Variant 9-21817755-A-G is Benign according to our data. Variant chr9-21817755-A-G is described in ClinVar as [Benign]. Clinvar id is 1221697.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.806 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTAP	NM_002451.4	c.180-280A>G		intron_variant		ENST00000644715.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTAP	ENST00000644715.2	c.180-280A>G		intron_variant			NM_002451.4	P1

Frequencies

GnomAD3 genomes AF: 0.623 AC: 94538 AN: 151798 Hom.: 30657 Cov.: 31

Gnomad AFR AF: 0.813

Gnomad AMI AF: 0.536

Gnomad AMR AF: 0.613

Gnomad ASJ AF: 0.547

Gnomad EAS AF: 0.774

Gnomad SAS AF: 0.411

Gnomad FIN AF: 0.576

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.527

Gnomad OTH AF: 0.589

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

GnomAD4 genome AF: 0.623 AC: 94656 AN: 151918 Hom.: 30711 Cov.: 31 AF XY: 0.620 AC XY: 46039 AN XY: 74234

Gnomad4 AFR AF: 0.813

Gnomad4 AMR AF: 0.613

Gnomad4 ASJ AF: 0.547

Gnomad4 EAS AF: 0.773

Gnomad4 SAS AF: 0.412

Gnomad4 FIN AF: 0.576

Gnomad4 NFE AF: 0.527

Gnomad4 OTH AF: 0.591

Alfa AF: 0.578 Hom.: 8938

Bravo AF: 0.643

Asia WGS AF: 0.607 AC: 2108 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	-0.98
Cadd	Benign	5.4
Dann	Benign	0.36

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: rs7027989; hg19: chr9-21817754;