Variant rs10965163 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002451.4(MTAP):c.561C>T(p.Arg187=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0804 in 1,614,066 control chromosomes in the GnomAD database, including 5,832 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.060 ( 376 hom., cov: 33)

Exomes 𝑓: 0.083 ( 5456 hom. )

Consequence

MTAP
NM_002451.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.0730

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 9-21854741-C-T is Benign according to our data. Variant chr9-21854741-C-T is described in ClinVar as [Benign]. Clinvar id is 366244.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.073 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0853 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.561C>T	p.Arg187=	synonymous_variant	6/8	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.561C>T	p.Arg187=	synonymous_variant	6/8		NM_002451.4	ENSP00000494373	P1	Q13126-1

Frequencies

GnomAD3 genomes

AF:

0.0597

AC:

9084

AN:

152164

Hom.:

376

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0169

Gnomad AMI

AF:

0.0208

Gnomad AMR

AF:

0.0712

Gnomad ASJ

AF:

0.130

Gnomad EAS

AF:

0.0341

Gnomad SAS

AF:

0.0441

Gnomad FIN

AF:

0.0312

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.0871

Gnomad OTH

AF:

0.0763

GnomAD3 exomes

AF:

0.0642

AC:

16140

AN:

251234

Hom.:

669

AF XY:

0.0658

AC XY:

8931

AN XY:

135776

show subpopulations

Gnomad AFR exome

AF:

0.0143

Gnomad AMR exome

AF:

0.0560

Gnomad ASJ exome

AF:

0.127

Gnomad EAS exome

AF:

0.0196

Gnomad SAS exome

AF:

0.0440

Gnomad FIN exome

AF:

0.0349

Gnomad NFE exome

AF:

0.0860

Gnomad OTH exome

AF:

0.0745

GnomAD4 exome

AF:

0.0826

AC:

120694

AN:

1461784

Hom.:

5456

Cov.:

AF XY:

0.0818

AC XY:

59462

AN XY:

727184

show subpopulations

Gnomad4 AFR exome

AF:

0.0140

Gnomad4 AMR exome

AF:

0.0573

Gnomad4 ASJ exome

AF:

0.125

Gnomad4 EAS exome

AF:

0.0487

Gnomad4 SAS exome

AF:

0.0468

Gnomad4 FIN exome

AF:

0.0364

Gnomad4 NFE exome

AF:

0.0913

Gnomad4 OTH exome

AF:

0.0758

GnomAD4 genome

AF:

0.0596

AC:

9082

AN:

152282

Hom.:

376

Cov.:

AF XY:

0.0588

AC XY:

4375

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.0169

Gnomad4 AMR

AF:

0.0711

Gnomad4 ASJ

AF:

0.130

Gnomad4 EAS

AF:

0.0342

Gnomad4 SAS

AF:

0.0439

Gnomad4 FIN

AF:

0.0312

Gnomad4 NFE

AF:

0.0871

Gnomad4 OTH

AF:

0.0755

Alfa

AF:

0.0849

Hom.:

1035

Bravo

AF:

0.0602

Asia WGS

AF:

0.0280

AC:

AN:

3478

EpiCase

AF:

0.0924

EpiControl

AF:

0.0909

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Diaphyseal medullary stenosis-bone malignancy syndrome

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	KCCC/NGS Laboratory, Kuwait Cancer Control Center	Jul 07, 2023	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 09, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

7.3

DANN

Benign

0.88

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