rs7874112

chr9-21832743-A-Gchr9-21832743-A-T

Variant summary

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

The NM_002451.4(MTAP):c.348-5165A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 152,052 control chromosomes in the GnomAD database, including 5,850 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 0.23 (5850 hom., cov: 32)
• Consequence: MTAP NM_002451.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.823

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.467 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTAP	NM_002451.4	c.348-5165A>G		intron_variant		ENST00000644715.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTAP	ENST00000644715.2	c.348-5165A>G		intron_variant			NM_002451.4	P1

Frequencies

GnomAD3 genomes AF: 0.231 AC: 35044 AN: 151934 Hom.: 5847 Cov.: 32

Gnomad AFR AF: 0.473

Gnomad AMI AF: 0.331

Gnomad AMR AF: 0.195

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.262

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.125

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.209

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

GnomAD4 genome AF: 0.231 AC: 35059 AN: 152052 Hom.: 5850 Cov.: 32 AF XY: 0.227 AC XY: 16858 AN XY: 74344

Gnomad4 AFR AF: 0.472

Gnomad4 AMR AF: 0.195

Gnomad4 ASJ AF: 0.159

Gnomad4 EAS AF: 0.262

Gnomad4 SAS AF: 0.163

Gnomad4 FIN AF: 0.125

Gnomad4 NFE AF: 0.113

Gnomad4 OTH AF: 0.206

Alfa AF: 0.141 Hom.: 1082

Bravo AF: 0.251

Asia WGS AF: 0.236 AC: 819 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	1.4
Dann	Benign	0.49

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: rs7874112; hg19: chr9-21832742;