9-21804618-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002451.4(MTAP):c.33+1837A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.612 in 152,086 control chromosomes in the GnomAD database, including 29,950 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 0.61 (29950 hom., cov: 32)
• Consequence: MTAP NM_002451.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.395

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.818 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTAP	NM_002451.4	c.33+1837A>G		intron_variant		ENST00000644715.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTAP	ENST00000644715.2	c.33+1837A>G		intron_variant			NM_002451.4	P1

Frequencies

GnomAD3 genomes AF: 0.612 AC: 92949 AN: 151966 Hom.: 29888 Cov.: 32

Gnomad AFR AF: 0.825

Gnomad AMI AF: 0.409

Gnomad AMR AF: 0.600

Gnomad ASJ AF: 0.530

Gnomad EAS AF: 0.708

Gnomad SAS AF: 0.379

Gnomad FIN AF: 0.512

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.518

Gnomad OTH AF: 0.580

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

GnomAD4 genome AF: 0.612 AC: 93082 AN: 152086 Hom.: 29950 Cov.: 32 AF XY: 0.607 AC XY: 45089 AN XY: 74334

Gnomad4 AFR AF: 0.825

Gnomad4 AMR AF: 0.601

Gnomad4 ASJ AF: 0.530

Gnomad4 EAS AF: 0.709

Gnomad4 SAS AF: 0.382

Gnomad4 FIN AF: 0.512

Gnomad4 NFE AF: 0.518

Gnomad4 OTH AF: 0.581

Alfa AF: 0.591 Hom.: 4081

Bravo AF: 0.637

Asia WGS AF: 0.557 AC: 1937 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	1.7
Dann	Benign	0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs869330; hg19: chr9-21804617;