Variant 9-21802923-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002451.4(MTAP):c.33+142C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0302 in 1,437,612 control chromosomes in the GnomAD database, including 1,054 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.024 ( 68 hom., cov: 28)

Exomes 𝑓: 0.031 ( 986 hom. )

Consequence

MTAP
NM_002451.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0110

Variant links:

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]

MTAP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 9-21802923-C-G is Benign according to our data. Variant chr9-21802923-C-G is described in ClinVar as [Benign]. Clinvar id is 1223355.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0758 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTAP	NM_002451.4 linkuse as main transcript	c.33+142C>G		intron_variant		ENST00000644715.2	NP_002442.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTAP	ENST00000644715.2 linkuse as main transcript	c.33+142C>G		intron_variant			NM_002451.4	ENSP00000494373	P1	Q13126-1

Frequencies

GnomAD3 genomes

AF:

0.0236

AC:

3513

AN:

149060

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00457

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0208

Gnomad ASJ

AF:

0.0275

Gnomad EAS

AF:

0.0826

Gnomad SAS

AF:

0.0771

Gnomad FIN

AF:

0.0370

Gnomad MID

AF:

0.00962

Gnomad NFE

AF:

0.0257

Gnomad OTH

AF:

0.0256

GnomAD3 exomes

AF:

0.0364

AC:

1731

AN:

47538

Hom.:

AF XY:

0.0391

AC XY:

988

AN XY:

25240

show subpopulations

Gnomad AFR exome

AF:

0.00396

Gnomad AMR exome

AF:

0.0137

Gnomad ASJ exome

AF:

0.0303

Gnomad EAS exome

AF:

0.0770

Gnomad SAS exome

AF:

0.0846

Gnomad FIN exome

AF:

0.0325

Gnomad NFE exome

AF:

0.0265

Gnomad OTH exome

AF:

0.0320

GnomAD4 exome

AF:

0.0310

AC:

39939

AN:

1288436

Hom.:

986

Cov.:

AF XY:

0.0325

AC XY:

20465

AN XY:

630306

show subpopulations

Gnomad4 AFR exome

AF:

0.00298

Gnomad4 AMR exome

AF:

0.0141

Gnomad4 ASJ exome

AF:

0.0314

Gnomad4 EAS exome

AF:

0.111

Gnomad4 SAS exome

AF:

0.0775

Gnomad4 FIN exome

AF:

0.0348

Gnomad4 NFE exome

AF:

0.0263

Gnomad4 OTH exome

AF:

0.0357

GnomAD4 genome

AF:

0.0235

AC:

3508

AN:

149176

Hom.:

Cov.:

AF XY:

0.0254

AC XY:

1842

AN XY:

72636

show subpopulations

Gnomad4 AFR

AF:

0.00456

Gnomad4 AMR

AF:

0.0208

Gnomad4 ASJ

AF:

0.0275

Gnomad4 EAS

AF:

0.0824

Gnomad4 SAS

AF:

0.0767

Gnomad4 FIN

AF:

0.0370

Gnomad4 NFE

AF:

0.0257

Gnomad4 OTH

AF:

0.0258

Alfa

AF:

0.0243

Hom.:

Bravo

AF:

0.0196

Asia WGS

AF:

0.0900

AC:

312

AN:

3466

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 21, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

8.2

DANN

Benign

0.73

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over