9-21815798-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002451.4(MTAP):c.120+279C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 152,026 control chromosomes in the GnomAD database, including 2,981 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.18 (2981 hom., cov: 31)
• Consequence: MTAP NM_002451.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.52

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 9-21815798-C-T is Benign according to our data. Variant chr9-21815798-C-T is described in ClinVar as [Benign]. Clinvar id is 1238889.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.295 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTAP	NM_002451.4	c.120+279C>T		intron_variant		ENST00000644715.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTAP	ENST00000644715.2	c.120+279C>T		intron_variant			NM_002451.4	P1

Frequencies

GnomAD3 genomes AF: 0.178 AC: 27016 AN: 151908 Hom.: 2980 Cov.: 31

Gnomad AFR AF: 0.299

Gnomad AMI AF: 0.330

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.265

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.170

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

GnomAD4 genome AF: 0.178 AC: 27039 AN: 152026 Hom.: 2981 Cov.: 31 AF XY: 0.177 AC XY: 13189 AN XY: 74322

Gnomad4 AFR AF: 0.299

Gnomad4 AMR AF: 0.180

Gnomad4 ASJ AF: 0.159

Gnomad4 EAS AF: 0.264

Gnomad4 SAS AF: 0.161

Gnomad4 FIN AF: 0.121

Gnomad4 NFE AF: 0.106

Gnomad4 OTH AF: 0.168

Alfa AF: 0.127 Hom.: 694

Bravo AF: 0.192

Asia WGS AF: 0.233 AC: 809 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.065
Dann	Benign	0.28

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: rs2282245; hg19: chr9-21815797;