NM_002451.4:c.34-266G>T

Variant names:

• chr9-21815167-G-T
• rs2039971
• NM_002451.4:c.34-266G>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002451.4(MTAP):​c.34-266G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 152,136 control chromosomes in the GnomAD database, including 1,432 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.11 (1432 hom., cov: 33)
• Consequence: MTAP NM_002451.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.215
• Publications: 8 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 9-21815167-G-T is Benign according to our data. Variant chr9-21815167-G-T is described in ClinVar as [Benign]. Clinvar id is 1276108.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTAP	NM_002451.4	c.34-266G>T		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.34-266G>T		intron_variant	Intron 1 of 7		NM_002451.4	ENSP00000494373.1

Frequencies

GnomAD3 genomes AF: 0.112 AC: 17060 AN: 152016 Hom.: 1430 Cov.: 33

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.0902

Gnomad EAS AF: 0.244

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.0854

Gnomad MID AF: 0.124

Gnomad NFE AF: 0.0443

Gnomad OTH AF: 0.100

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.112 AC: 17067 AN: 152136 Hom.: 1432 Cov.: 33 AF XY: 0.114 AC XY: 8496 AN XY: 74374

African (AFR) AF: 0.206 AC: 8557 AN: 41474

American (AMR) AF: 0.135 AC: 2058 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0902 AC: 313 AN: 3470

East Asian (EAS) AF: 0.244 AC: 1260 AN: 5172

South Asian (SAS) AF: 0.116 AC: 559 AN: 4826

European-Finnish (FIN) AF: 0.0854 AC: 904 AN: 10590

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.0443 AC: 3012 AN: 68002

Other (OTH) AF: 0.0993 AC: 210 AN: 2114

Alfa AF: 0.0649 Hom.: 999

Bravo AF: 0.123

Asia WGS AF: 0.169 AC: 586 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.8
DANN	Benign	0.44
PhyloP100		-0.21
Mutation Taster		=100/0	polymorphism (auto)

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: rs2039971; hg19: chr9-21815166;