9-21815590-TA-T

Variant names:

• chr9-21815590-TA-T
• rs4007652
• NM_002451.4:c.120+85delA

Variant summary

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

The NM_002451.4(MTAP):​c.120+85delA variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.000027 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0020 (0 hom.)
• 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+85delA		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+85delA		intron_variant	Intron 2 of 7		NM_002451.4	ENSP00000494373.1

Frequencies

GnomAD3 genomes AF: 0.0000274 AC: 4 AN: 146242 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: 0.000231

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000299

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00284 AC: 243 AN: 85622 AF XY: 0.00274

Gnomad AFR exome AF: 0.00214

Gnomad AMR exome AF: 0.00437

Gnomad ASJ exome AF: 0.00387

Gnomad EAS exome AF: 0.000375

Gnomad FIN exome AF: 0.000732

Gnomad NFE exome AF: 0.00386

Gnomad OTH exome AF: 0.00367

GnomAD4 exome AF: 0.00204 AC: 1247 AN: 610428 Hom.: 0 Cov.: 12 AF XY: 0.00189 AC XY: 613 AN XY: 325066

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

African (AFR) AF: 0.00115 AC: 15 AN: 13006

American (AMR) AF: 0.00260 AC: 52 AN: 20022

Ashkenazi Jewish (ASJ) AF: 0.00219 AC: 38 AN: 17382

East Asian (EAS) AF: 0.000475 AC: 13 AN: 27366

South Asian (SAS) AF: 0.000696 AC: 37 AN: 53158

European-Finnish (FIN) AF: 0.000896 AC: 39 AN: 43528

Middle Eastern (MID) AF: 0.00209 AC: 5 AN: 2390

European-Non Finnish (NFE) AF: 0.00244 AC: 985 AN: 403890

Other (OTH) AF: 0.00212 AC: 63 AN: 29686

⚠️ 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 AF: 0.0000274 AC: 4 AN: 146242 Hom.: 0 Cov.: 0 AF XY: 0.0000565 AC XY: 4 AN XY: 70770

African (AFR) AF: 0.00 AC: 0 AN: 39670

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: 0.000231 AC: 2 AN: 8664

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

European-Non Finnish (NFE) AF: 0.0000299 AC: 2 AN: 66908

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

Alfa AF: 0.00395 Hom.: 233

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.53
Mutation Taster		=100/0	polymorphism

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Other links and lift over

dbSNP: rs4007652; hg19: chr9-21815589;