NM_002451.4:c.*2085G>T

Variant names:

• chr9-21864099-G-T
• rs10117507
• NM_002451.4:c.*2085G>T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_002451.4(MTAP):​c.*2085G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000108 in 833,118 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: 32)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: MTAP NM_002451.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.681

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

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BS2: High AC in GnomAdExome4 at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTAP	NM_002451.4	c.*2085G>T		3_prime_UTR_variant	Exon 8 of 8	ENST00000644715.2	NP_002442.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTAP	ENST00000644715.2	c.*2085G>T		3_prime_UTR_variant	Exon 8 of 8		NM_002451.4	ENSP00000494373.1
MTAP	ENST00000580900.5	c.813+4674G>T		intron_variant	Intron 7 of 7	1		ENSP00000463424.1
MTAP	ENST00000577563.1	c.147+9229G>T		intron_variant	Intron 1 of 1	1		ENSP00000462082.1
ENSG00000264545	ENST00000404796.3	n.460+45897G>T		intron_variant	Intron 4 of 4	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000108 AC: 9 AN: 833118 Hom.: 0 Cov.: 35 AF XY: 0.0000156 AC XY: 6 AN XY: 384722

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000105

Gnomad4 OTH exome AF: 0.0000366

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.32
DANN	Benign	0.40

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

LitVar

Other links and lift over

dbSNP: rs10117507; hg19: chr9-21864098;