rs4478653

chr9-21853222-T-C

Variant summary

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

The NM_002451.4(MTAP):c.451-1409T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.527 in 151,784 control chromosomes in the GnomAD database, including 22,802 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 0.53 (22802 hom., cov: 31)
• Consequence: MTAP NM_002451.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.68

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 (EAS) allele frequency at 95% confidence interval = 0.718 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTAP	NM_002451.4	c.451-1409T>C		intron_variant		ENST00000644715.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTAP	ENST00000644715.2	c.451-1409T>C		intron_variant			NM_002451.4	P1

Frequencies

GnomAD3 genomes AF: 0.527 AC: 79908 AN: 151666 Hom.: 22752 Cov.: 31

Gnomad AFR AF: 0.715

Gnomad AMI AF: 0.525

Gnomad AMR AF: 0.586

Gnomad ASJ AF: 0.419

Gnomad EAS AF: 0.739

Gnomad SAS AF: 0.474

Gnomad FIN AF: 0.510

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.397

Gnomad OTH AF: 0.492

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

GnomAD4 genome AF: 0.527 AC: 80018 AN: 151784 Hom.: 22802 Cov.: 31 AF XY: 0.531 AC XY: 39392 AN XY: 74158

Gnomad4 AFR AF: 0.716

Gnomad4 AMR AF: 0.586

Gnomad4 ASJ AF: 0.419

Gnomad4 EAS AF: 0.738

Gnomad4 SAS AF: 0.476

Gnomad4 FIN AF: 0.510

Gnomad4 NFE AF: 0.397

Gnomad4 OTH AF: 0.496

Alfa AF: 0.415 Hom.: 27666

Bravo AF: 0.550

Asia WGS AF: 0.614 AC: 2138 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	0.55
Dann	Benign	0.46

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: rs4478653; hg19: chr9-21853221;