Genetic Variant MTAP:c.120+79_120+85dupAAAAAAA (chr9-21815590-T-TAAAAAAA) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_002451.4(MTAP):c.120+79_120+85dupAAAAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000096 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0000049 ( 0 hom. )

Consequence

MTAP
NM_002451.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.529

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:

ENSG00000264545 (HGNC:):

ENSG00000264545 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAd4 at 14 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTAP	NM_002451.4 link	c.120+79_120+85dupAAAAAAA		intron_variant	Intron 2 of 7	ENST00000644715.2	NP_002442.2	Q13126-1A0A384ME80

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTAP	ENST00000644715.2 link	c.120+79_120+85dupAAAAAAA		intron_variant	Intron 2 of 7		NM_002451.4	ENSP00000494373.1		Q13126-1

Frequencies

GnomAD3 genomes

AF:

0.0000889

AC:

AN:

146238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000303

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000679

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000490

AC:

AN:

611632

Hom.:

Cov.:

AF XY:

0.00000921

AC XY:

AN XY:

325732

show subpopulations

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

African (AFR)

AF:

0.0000768

AC:

AN:

13022

American (AMR)

AF:

0.00

AC:

AN:

20060

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17424

East Asian (EAS)

AF:

0.00

AC:

AN:

27438

South Asian (SAS)

AF:

0.00

AC:

AN:

53214

European-Finnish (FIN)

AF:

0.00

AC:

AN:

43608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2392

European-Non Finnish (NFE)

AF:

0.00000494

AC:

AN:

404740

Other (OTH)

AF:

0.00

AC:

AN:

29734

⚠️ 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: 0.242

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000957

AC:

AN:

146296

Hom.:

Cov.:

AF XY:

0.0000847

AC XY:

AN XY:

70846

show subpopulations

African (AFR)

AF:

0.000327

AC:

AN:

39760

American (AMR)

AF:

0.0000679

AC:

AN:

14736

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3444

East Asian (EAS)

AF:

0.00

AC:

AN:

4994

South Asian (SAS)

AF:

0.00

AC:

AN:

4588

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8664

Middle Eastern (MID)

AF:

0.00

AC:

AN:

284

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

66898

Other (OTH)

AF:

0.00

AC:

AN:

2018

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

233

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.53

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Loading publications...

chr9-21815590-T-TAAAAAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over