Genetic Variant ENST00000580900.5:c.*698G>T (chr9-21931897-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000580900.5(MTAP):c.*698G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.387 in 152,040 control chromosomes in the GnomAD database, including 15,259 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 0.39 ( 15259 hom., cov: 32)

Exomes 𝑓: 0.20 ( 0 hom. )

Consequence

MTAP
ENST00000580900.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.665

Publications

2 publications found

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 Gene-Disease associations (from GenCC):

diaphyseal medullary stenosis-bone malignancy syndrome
Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: Genomics England PanelApp, G2P, Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen

MTAP links:

ENSG00000264545 (HGNC:):

ENSG00000264545 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.02).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.713 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein
MTAP	NM_001396041.1 link	c.*698G>T	3_prime_UTR_variant	Exon 8 of 8	NP_001382970.1
MTAP	NM_001396044.1 link	c.922+781G>T	intron_variant	Intron 8 of 9	NP_001382973.1
MTAP	NM_001396045.1 link	c.799+781G>T	intron_variant	Intron 7 of 8	NP_001382974.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
MTAP	ENST00000580900.5 link	c.*698G>T	3_prime_UTR_variant	Exon 8 of 8	1	ENSP00000463424.1	Q13126-3
MTAP	ENST00000616982.1 link	n.1508G>T	non_coding_transcript_exon_variant	Exon 1 of 1	6
ENSG00000264545	ENST00000404796.3 link	n.461-97536G>T	intron_variant	Intron 4 of 4	5

Frequencies

GnomAD3 genomes

AF:

0.386

AC:

58664

AN:

151912

Hom.:

15207

Cov.:

show subpopulations

Gnomad AFR

AF:

0.719

Gnomad AMI

AF:

0.357

Gnomad AMR

AF:

0.414

Gnomad ASJ

AF:

0.233

Gnomad EAS

AF:

0.543

Gnomad SAS

AF:

0.340

Gnomad FIN

AF:

0.266

Gnomad MID

AF:

0.247

Gnomad NFE

AF:

0.198

Gnomad OTH

AF:

0.344

GnomAD4 exome

AF:

0.200

AC:

AN:

Hom.:

Cov.:

AF XY:

0.125

AC XY:

AN XY:

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.200

AC:

AN:

Other (OTH)

AC:

AN:

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.325

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.387

AC:

58784

AN:

152030

Hom.:

15259

Cov.:

AF XY:

0.390

AC XY:

28982

AN XY:

74314

show subpopulations

African (AFR)

AF:

0.720

AC:

29837

AN:

41456

American (AMR)

AF:

0.415

AC:

6336

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.233

AC:

808

AN:

3470

East Asian (EAS)

AF:

0.543

AC:

2804

AN:

5164

South Asian (SAS)

AF:

0.339

AC:

1635

AN:

4818

European-Finnish (FIN)

AF:

0.266

AC:

2805

AN:

10548

Middle Eastern (MID)

AF:

0.241

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.198

AC:

13429

AN:

67984

Other (OTH)

AF:

0.347

AC:

733

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1439

2878

4317

5756

7195

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

496

992

1488

1984

2480

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.388

Hom.:

2738

Bravo

AF:

0.417

Asia WGS

AF:

0.465

AC:

1618

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.85

(source)

DANN

Benign

0.35

PhyloP100

-0.67

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over