dbSNP rs949068748: MTAP:c.-52G>C (chr9-21802697-G-C) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_002451.4(MTAP):c.-52G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000155 in 1,590,122 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 29)

Exomes 𝑓: 0.00016 ( 1 hom. )

Consequence

MTAP
NM_002451.4 5_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.59

Publications

0 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: ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, Genomics England PanelApp, Orphanet

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BS2

High AC in GnomAd4 at 11 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002451.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MTAP	NM_002451.4	MANE Select	c.-52G>C	5_prime_UTR	Exon 1 of 8	NP_002442.2
MTAP	NM_001396044.1		c.-52G>C	5_prime_UTR	Exon 1 of 10	NP_001382973.1	Q13126-2
MTAP	NM_001396041.1		c.-52G>C	5_prime_UTR	Exon 1 of 8	NP_001382970.1	Q13126-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MTAP	ENST00000644715.2	MANE Select	c.-52G>C	5_prime_UTR	Exon 1 of 8	ENSP00000494373.1	Q13126-1
MTAP	ENST00000580900.5	TSL:1	c.-52G>C	5_prime_UTR	Exon 1 of 8	ENSP00000463424.1	Q13126-3
MTAP	ENST00000580718.1	TSL:1	n.-52G>C	non_coding_transcript_exon	Exon 1 of 8	ENSP00000464616.1	J3QSB7

Frequencies

GnomAD3 genomes

AF:

0.0000724

AC:

AN:

152012

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000164

AC:

236

AN:

1438110

Hom.:

Cov.:

AF XY:

0.000162

AC XY:

116

AN XY:

713878

show subpopulations

African (AFR)

AF:

0.0000305

AC:

AN:

32784

American (AMR)

AF:

0.00

AC:

AN:

41186

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25908

East Asian (EAS)

AF:

0.00

AC:

AN:

38168

South Asian (SAS)

AF:

0.00

AC:

AN:

83082

European-Finnish (FIN)

AF:

0.0000197

AC:

AN:

50828

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5172

European-Non Finnish (NFE)

AF:

0.000209

AC:

230

AN:

1101558

Other (OTH)

AF:

0.0000673

AC:

AN:

59424

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.0000724

AC:

AN:

152012

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74240

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41406

American (AMR)

AF:

0.00

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5130

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000147

AC:

AN:

67996

Other (OTH)

AF:

0.00

AC:

AN:

2082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000270

Hom.:

Bravo

AF:

0.0000945

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Diaphyseal medullary stenosis-bone malignancy syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

2.2

(source)

DANN

Benign

0.37

PhyloP100

-1.6

PromoterAI

0.15

Neutral

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over