9-21815590-TAAAAA-TAAA

Variant names:

• chr9-21815590-TAA-T
• rs4007652
• NM_002451.4:c.120+84_120+85delAA

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_002451.4(MTAP):​c.120+84_120+85delAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000965 in 611,468 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000096 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MTAP NM_002451.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.529

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: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTAP	NM_002451.4	c.120+84_120+85delAA		intron_variant	Intron 2 of 7	ENST00000644715.2	NP_002442.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTAP	ENST00000644715.2	c.120+84_120+85delAA		intron_variant	Intron 2 of 7		NM_002451.4	ENSP00000494373.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 146252 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000965 AC: 59 AN: 611468 Hom.: 0 AF XY: 0.0000891 AC XY: 29 AN XY: 325634

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

African (AFR) AF: 0.0000768 AC: 1 AN: 13016

American (AMR) AF: 0.000150 AC: 3 AN: 20048

Ashkenazi Jewish (ASJ) AF: 0.000115 AC: 2 AN: 17422

East Asian (EAS) AF: 0.0000365 AC: 1 AN: 27430

South Asian (SAS) AF: 0.0000752 AC: 4 AN: 53204

European-Finnish (FIN) AF: 0.0000229 AC: 1 AN: 43592

Middle Eastern (MID) AF: 0.000418 AC: 1 AN: 2392

European-Non Finnish (NFE) AF: 0.000104 AC: 42 AN: 404630

Other (OTH) AF: 0.000135 AC: 4 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.

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 146252 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 70778

African (AFR) AF: 0.00 AC: 0 AN: 39672

American (AMR) AF: 0.00 AC: 0 AN: 14726

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3444

East Asian (EAS) AF: 0.00 AC: 0 AN: 5002

South Asian (SAS) AF: 0.00 AC: 0 AN: 4612

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8666

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 308

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66914

Other (OTH) AF: 0.00 AC: 0 AN: 1998

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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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Other links and lift over

dbSNP: rs4007652; hg19: chr9-21815589;