rs7869004

Positions:

• chr9-21931897-G-T

Variant summary

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

The ENST00000580900.5(MTAP):​c.*698G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.387 in 152,040 control chromosomes in the GnomAD database, including 15,259 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 0.39 (15259 hom., cov: 32)
  • Exomes 𝑓: 0.20 (0 hom.)
• Consequence: MTAP ENST00000580900.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.665

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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.713 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTAP	NM_001396041.1	c.*698G>T		3_prime_UTR_variant	8/8		NP_001382970.1
MTAP	NM_001396042.1	c.691-7263G>T		intron_variant			NP_001382971.1
MTAP	NM_001396043.1	c.814-7263G>T		intron_variant			NP_001382972.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTAP	ENST00000580900.5	c.*698G>T		3_prime_UTR_variant	8/8	1		ENSP00000463424
MTAP	ENST00000616982.1	n.1508G>T		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.386 AC: 58664 AN: 151912 Hom.: 15207 Cov.: 32

Gnomad AFR AF: 0.719

Gnomad AMI AF: 0.357

Gnomad AMR AF: 0.414

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.543

Gnomad SAS AF: 0.340

Gnomad FIN AF: 0.266

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.198

Gnomad OTH AF: 0.344

GnomAD4 exome AF: 0.200 AC: 2 AN: 10 Hom.: 0 Cov.: 0 AF XY: 0.125 AC XY: 1 AN XY: 8

Gnomad4 NFE exome AF: 0.200

GnomAD4 genome AF: 0.387 AC: 58784 AN: 152030 Hom.: 15259 Cov.: 32 AF XY: 0.390 AC XY: 28982 AN XY: 74314

Gnomad4 AFR AF: 0.720

Gnomad4 AMR AF: 0.415

Gnomad4 ASJ AF: 0.233

Gnomad4 EAS AF: 0.543

Gnomad4 SAS AF: 0.339

Gnomad4 FIN AF: 0.266

Gnomad4 NFE AF: 0.198

Gnomad4 OTH AF: 0.347

Alfa AF: 0.379 Hom.: 2542

Bravo AF: 0.417

Asia WGS AF: 0.465 AC: 1618 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.85
DANN	Benign	0.35

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: rs7869004; hg19: chr9-21931896;