9-21802640-GCACTGC-G

Variant names:

• chr9-21802640-GCACTGC-G
• rs886063780
• NM_002451.4:c.-108_-103delCACTGC

Variant summary

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

The NM_002451.4(MTAP):​c.-108_-103delCACTGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000947 in 1,267,320 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 29)
  • Exomes 𝑓: 0.0000090 (0 hom.)
• Consequence: MTAP NM_002451.4 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.09

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]

ENSG00000264545 (HGNC:):

ACMG classification

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

• BS2: High AC in GnomAdExome4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTAP	NM_002451.4	c.-108_-103delCACTGC		5_prime_UTR_variant	Exon 1 of 8	ENST00000644715.2	NP_002442.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTAP	ENST00000644715.2	c.-108_-103delCACTGC		5_prime_UTR_variant	Exon 1 of 8		NM_002451.4	ENSP00000494373.1

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151944 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000897 AC: 10 AN: 1115376 Hom.: 0 AF XY: 0.00000708 AC XY: 4 AN XY: 565024

African (AFR) AF: 0.00 AC: 0 AN: 24570

American (AMR) AF: 0.00 AC: 0 AN: 36984

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23200

East Asian (EAS) AF: 0.0000290 AC: 1 AN: 34512

South Asian (SAS) AF: 0.00 AC: 0 AN: 74064

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49988

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3772

European-Non Finnish (NFE) AF: 0.00000122 AC: 1 AN: 819726

Other (OTH) AF: 0.000165 AC: 8 AN: 48560

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151944 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 74210

African (AFR) AF: 0.00 AC: 0 AN: 41376

American (AMR) AF: 0.0000655 AC: 1 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5124

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67968

Other (OTH) AF: 0.00 AC: 0 AN: 2082

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Diaphyseal medullary stenosis-bone malignancy syndrome Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.1

Splicing

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

Publications

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Other links and lift over

dbSNP: rs886063780; hg19: chr9-21802639;