Variant rs10117507 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.*2085G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 985,148 control chromosomes in the GnomAD database, including 21,816 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 4844 hom., cov: 32)

Exomes 𝑓: 0.20 ( 16972 hom. )

Consequence

MTAP
NM_002451.4 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.681

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=-0.91).

BP6

Variant 9-21864099-G-A is Benign according to our data. Variant chr9-21864099-G-A is described in ClinVar as [Benign]. Clinvar id is 366288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.369 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.*2085G>A		3_prime_UTR_variant	8/8	ENST00000644715.2	NP_002442.2

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTAP	ENST00000644715.2 linkuse as main transcript	c.*2085G>A	3_prime_UTR_variant	8/8		NM_002451.4	ENSP00000494373	P1	Q13126-1
MTAP	ENST00000577563.1 linkuse as main transcript	c.147+9229G>A	intron_variant		1		ENSP00000462082
MTAP	ENST00000580900.5 linkuse as main transcript	c.813+4674G>A	intron_variant		1		ENSP00000463424		Q13126-3

Frequencies

GnomAD3 genomes

AF:

0.243

AC:

36980

AN:

151974

Hom.:

4816

Cov.:

show subpopulations

Gnomad AFR

AF:

0.248

Gnomad AMI

AF:

0.346

Gnomad AMR

AF:

0.368

Gnomad ASJ

AF:

0.218

Gnomad EAS

AF:

0.383

Gnomad SAS

AF:

0.239

Gnomad FIN

AF:

0.216

Gnomad MID

AF:

0.247

Gnomad NFE

AF:

0.206

Gnomad OTH

AF:

0.255

GnomAD4 exome

AF:

0.200

AC:

166336

AN:

833056

Hom.:

16972

Cov.:

AF XY:

0.199

AC XY:

76675

AN XY:

384690

show subpopulations

Gnomad4 AFR exome

AF:

0.253

Gnomad4 AMR exome

AF:

0.422

Gnomad4 ASJ exome

AF:

0.215

Gnomad4 EAS exome

AF:

0.389

Gnomad4 SAS exome

AF:

0.244

Gnomad4 FIN exome

AF:

0.218

Gnomad4 NFE exome

AF:

0.196

Gnomad4 OTH exome

AF:

0.217

GnomAD4 genome

AF:

0.244

AC:

37061

AN:

152092

Hom.:

4844

Cov.:

AF XY:

0.248

AC XY:

18399

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.248

Gnomad4 AMR

AF:

0.369

Gnomad4 ASJ

AF:

0.218

Gnomad4 EAS

AF:

0.383

Gnomad4 SAS

AF:

0.239

Gnomad4 FIN

AF:

0.216

Gnomad4 NFE

AF:

0.206

Gnomad4 OTH

AF:

0.260

Alfa

AF:

0.212

Hom.:

3461

Bravo

AF:

0.258

Asia WGS

AF:

0.317

AC:

1102

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Diaphyseal medullary stenosis-bone malignancy syndrome

Benign:1

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. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.39

DANN

Benign

0.30

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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