9-21803881-C-A

Variant names:

• chr9-21803881-C-A
• rs871024
• NM_002451.4:c.33+1100C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002451.4(MTAP):​c.33+1100C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.611 in 152,012 control chromosomes in the GnomAD database, including 29,786 homozygotes. 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: 𝑓 0.61 (29786 hom., cov: 32)
• Consequence: MTAP NM_002451.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.223
• Publications: 7 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.812 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTAP	NM_002451.4	c.33+1100C>A		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.33+1100C>A		intron_variant	Intron 1 of 7		NM_002451.4	ENSP00000494373.1

Frequencies

GnomAD3 genomes AF: 0.611 AC: 92747 AN: 151892 Hom.: 29726 Cov.: 32

Gnomad AFR AF: 0.819

Gnomad AMI AF: 0.410

Gnomad AMR AF: 0.600

Gnomad ASJ AF: 0.530

Gnomad EAS AF: 0.711

Gnomad SAS AF: 0.388

Gnomad FIN AF: 0.514

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.518

Gnomad OTH AF: 0.579

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

GnomAD4 genome AF: 0.611 AC: 92875 AN: 152012 Hom.: 29786 Cov.: 32 AF XY: 0.606 AC XY: 45026 AN XY: 74300

African (AFR) AF: 0.819 AC: 33980 AN: 41466

American (AMR) AF: 0.600 AC: 9175 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.530 AC: 1838 AN: 3470

East Asian (EAS) AF: 0.711 AC: 3672 AN: 5164

South Asian (SAS) AF: 0.390 AC: 1879 AN: 4824

European-Finnish (FIN) AF: 0.514 AC: 5413 AN: 10538

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.518 AC: 35176 AN: 67956

Other (OTH) AF: 0.580 AC: 1223 AN: 2108

Alfa AF: 0.603 Hom.: 4087

Bravo AF: 0.635

Asia WGS AF: 0.566 AC: 1969 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.1
DANN	Benign	0.53
PhyloP100		-0.22
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs871024; hg19: chr9-21803880;