chr9-21802923-C-A

Variant names:

• chr9-21802923-C-A
• rs117769854
• NM_002451.4:c.33+142C>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_002451.4(MTAP):​c.33+142C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000109 in 1,288,448 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 28)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: MTAP NM_002451.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0110
• Publications: 0 publications found

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

ENSG00000264545 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BS2: High AC in GnomAdExome4 at 14 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTAP	NM_002451.4	c.33+142C>A		intron_variant	Intron 1 of 7	ENST00000644715.2	NP_002442.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTAP	ENST00000644715.2	c.33+142C>A		intron_variant	Intron 1 of 7		NM_002451.4	ENSP00000494373.1

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD2 exomes AF: 0.0000210 AC: 1 AN: 47538 AF XY: 0.0000396

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000493

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000109 AC: 14 AN: 1288448 Hom.: 0 Cov.: 32 AF XY: 0.00000952 AC XY: 6 AN XY: 630314

African (AFR) AF: 0.0000387 AC: 1 AN: 25822

American (AMR) AF: 0.00 AC: 0 AN: 18236

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18512

East Asian (EAS) AF: 0.00 AC: 0 AN: 33024

South Asian (SAS) AF: 0.00 AC: 0 AN: 62096

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33956

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3664

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1039738

Other (OTH) AF: 0.000243 AC: 13 AN: 53400

GnomAD4 genome Cov.: 28

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	7.7
DANN	Benign	0.88
PhyloP100		0.011
PromoterAI		-0.015	Neutral

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

Other links and lift over

dbSNP: rs117769854; hg19: chr9-21802922;