9-21802923-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002451.4(MTAP):c.33+142C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0302 in 1,437,612 control chromosomes in the GnomAD database, including 1,054 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.024 (68 hom., cov: 28)
  • Exomes 𝑓: 0.031 (986 hom.)
• Consequence: MTAP NM_002451.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0110

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 9-21802923-C-G is Benign according to our data. Variant chr9-21802923-C-G is described in ClinVar as [Benign]. Clinvar id is 1223355.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0758 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTAP	NM_002451.4	c.33+142C>G		intron_variant		ENST00000644715.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTAP	ENST00000644715.2	c.33+142C>G		intron_variant			NM_002451.4	P1

Frequencies

GnomAD3 genomes AF: 0.0236 AC: 3513 AN: 149060 Hom.: 69 Cov.: 28

Gnomad AFR AF: 0.00457

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0208

Gnomad ASJ AF: 0.0275

Gnomad EAS AF: 0.0826

Gnomad SAS AF: 0.0771

Gnomad FIN AF: 0.0370

Gnomad MID AF: 0.00962

Gnomad NFE AF: 0.0257

Gnomad OTH AF: 0.0256

GnomAD3 exomes AF: 0.0364 AC: 1731 AN: 47538 Hom.: 68 AF XY: 0.0391 AC XY: 988 AN XY: 25240

Gnomad AFR exome AF: 0.00396

Gnomad AMR exome AF: 0.0137

Gnomad ASJ exome AF: 0.0303

Gnomad EAS exome AF: 0.0770

Gnomad SAS exome AF: 0.0846

Gnomad FIN exome AF: 0.0325

Gnomad NFE exome AF: 0.0265

Gnomad OTH exome AF: 0.0320

GnomAD4 exome AF: 0.0310 AC: 39939 AN: 1288436 Hom.: 986 Cov.: 32 AF XY: 0.0325 AC XY: 20465 AN XY: 630306

Gnomad4 AFR exome AF: 0.00298

Gnomad4 AMR exome AF: 0.0141

Gnomad4 ASJ exome AF: 0.0314

Gnomad4 EAS exome AF: 0.111

Gnomad4 SAS exome AF: 0.0775

Gnomad4 FIN exome AF: 0.0348

Gnomad4 NFE exome AF: 0.0263

Gnomad4 OTH exome AF: 0.0357

GnomAD4 genome AF: 0.0235 AC: 3508 AN: 149176 Hom.: 68 Cov.: 28 AF XY: 0.0254 AC XY: 1842 AN XY: 72636

Gnomad4 AFR AF: 0.00456

Gnomad4 AMR AF: 0.0208

Gnomad4 ASJ AF: 0.0275

Gnomad4 EAS AF: 0.0824

Gnomad4 SAS AF: 0.0767

Gnomad4 FIN AF: 0.0370

Gnomad4 NFE AF: 0.0257

Gnomad4 OTH AF: 0.0258

Alfa AF: 0.0243 Hom.: 9

Bravo AF: 0.0196

Asia WGS AF: 0.0900 AC: 312 AN: 3466

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 21, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	8.2
Dann	Benign	0.73

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: rs117769854; hg19: chr9-21802922;