rs4977746

Positions:

• chr9-21920347-T-C

Variant summary

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

The ENST00000580900.5(MTAP):​c.814-10661T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.381 in 152,032 control chromosomes in the GnomAD database, including 14,496 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 0.38 (14496 hom., cov: 31)
• Consequence: MTAP ENST00000580900.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.96

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.682 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTAP	NM_001396041.1	c.814-10661T>C		intron_variant			NP_001382970.1
MTAP	NM_001396042.1	c.691-18813T>C		intron_variant			NP_001382971.1
MTAP	NM_001396043.1	c.814-18813T>C		intron_variant			NP_001382972.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTAP	ENST00000577563.1	c.148-10661T>C		intron_variant		1		ENSP00000462082
MTAP	ENST00000580900.5	c.814-10661T>C		intron_variant		1		ENSP00000463424

Frequencies

GnomAD3 genomes AF: 0.381 AC: 57809 AN: 151912 Hom.: 14452 Cov.: 31

Gnomad AFR AF: 0.688

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.411

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.569

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.284

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.349

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

GnomAD4 genome AF: 0.381 AC: 57923 AN: 152032 Hom.: 14496 Cov.: 31 AF XY: 0.385 AC XY: 28573 AN XY: 74288

Gnomad4 AFR AF: 0.688

Gnomad4 AMR AF: 0.412

Gnomad4 ASJ AF: 0.237

Gnomad4 EAS AF: 0.568

Gnomad4 SAS AF: 0.344

Gnomad4 FIN AF: 0.284

Gnomad4 NFE AF: 0.199

Gnomad4 OTH AF: 0.352

Alfa AF: 0.229 Hom.: 9761

Bravo AF: 0.409

Asia WGS AF: 0.476 AC: 1656 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.4
DANN	Benign	0.40

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: rs4977746; hg19: chr9-21920346; COSMIC: COSV68684360;