Genetic Variant MTAP:c.814-860G>C (chr9-21930148-G-C) – 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.814-860G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 401,890 control chromosomes in the GnomAD database, including 27,988 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 0.38 ( 14891 hom., cov: 33)

Exomes 𝑓: 0.29 ( 13097 hom. )

Consequence

MTAP
ENST00000580900.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.671

Publications

3 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 links:

ERVFRD-3 (HGNC:49792): (endogenous retrovirus group FRD member 3)

ERVFRD-3 links:

ENSG00000264545 (HGNC:):

ENSG00000264545 links:

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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 = 0.706 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein
MTAP	NM_001396044.1 link	c.814-860G>C	intron_variant	Intron 7 of 9	NP_001382973.1
MTAP	NM_001396041.1 link	c.814-860G>C	intron_variant	Intron 7 of 7	NP_001382970.1
MTAP	NM_001396045.1 link	c.691-860G>C	intron_variant	Intron 6 of 8	NP_001382974.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein
MTAP	ENST00000580900.5 link	c.814-860G>C	intron_variant	Intron 7 of 7	1	ENSP00000463424.1
MTAP	ENST00000577563.1 link	c.148-860G>C	intron_variant	Intron 1 of 1	1	ENSP00000462082.1
ERVFRD-3	ENST00000578561.1 link	n.692G>C	non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes

AF:

0.383

AC:

58189

AN:

151946

Hom.:

14843

Cov.:

show subpopulations

Gnomad AFR

AF:

0.713

Gnomad AMI

AF:

0.358

Gnomad AMR

AF:

0.410

Gnomad ASJ

AF:

0.235

Gnomad EAS

AF:

0.498

Gnomad SAS

AF:

0.334

Gnomad FIN

AF:

0.267

Gnomad MID

AF:

0.241

Gnomad NFE

AF:

0.198

Gnomad OTH

AF:

0.346

GnomAD4 exome

AF:

0.290

AC:

72375

AN:

249826

Hom.:

13097

Cov.:

AF XY:

0.284

AC XY:

40862

AN XY:

143730

show subpopulations

African (AFR)

AF:

0.722

AC:

5340

AN:

7392

American (AMR)

AF:

0.532

AC:

10640

AN:

19984

Ashkenazi Jewish (ASJ)

AF:

0.254

AC:

1763

AN:

6942

East Asian (EAS)

AF:

0.510

AC:

5496

AN:

10784

South Asian (SAS)

AF:

0.329

AC:

14175

AN:

43132

European-Finnish (FIN)

AF:

0.275

AC:

2944

AN:

10692

Middle Eastern (MID)

AF:

0.231

AC:

569

AN:

2462

European-Non Finnish (NFE)

AF:

0.205

AC:

28028

AN:

136418

Other (OTH)

AF:

0.285

AC:

3420

AN:

12020

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.533

Heterozygous variant carriers

2061

4122

6184

8245

10306

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

448

896

1344

1792

2240

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.383

AC:

58305

AN:

152064

Hom.:

14891

Cov.:

AF XY:

0.386

AC XY:

28689

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.713

AC:

29588

AN:

41484

American (AMR)

AF:

0.411

AC:

6272

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.235

AC:

815

AN:

3470

East Asian (EAS)

AF:

0.498

AC:

2576

AN:

5168

South Asian (SAS)

AF:

0.334

AC:

1609

AN:

4820

European-Finnish (FIN)

AF:

0.267

AC:

2828

AN:

10572

Middle Eastern (MID)

AF:

0.235

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.198

AC:

13488

AN:

67970

Other (OTH)

AF:

0.348

AC:

734

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1503

3006

4509

6012

7515

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

492

984

1476

1968

2460

<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:

0.176

Hom.:

409

Bravo

AF:

0.413

Asia WGS

AF:

0.437

AC:

1520

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

0.51

(source)

DANN

Benign

0.61

PhyloP100

-0.67

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over