rs7023474

chr9-21816647-A-Gchr9-21816647-A-T

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.121-67A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.556 in 1,408,308 control chromosomes in the GnomAD database, including 223,780 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.63 (31459 hom., cov: 32)
  • Exomes 𝑓: 0.55 (192321 hom.)
• Consequence: MTAP NM_002451.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.622

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=-0.84).
• BP6: Variant 9-21816647-A-G is Benign according to our data. Variant chr9-21816647-A-G is described in ClinVar as [Benign]. Clinvar id is 1239449.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.809 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTAP	NM_002451.4	c.121-67A>G		intron_variant		ENST00000644715.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTAP	ENST00000644715.2	c.121-67A>G		intron_variant			NM_002451.4	P1

Frequencies

GnomAD3 genomes AF: 0.632 AC: 96005 AN: 151874 Hom.: 31401 Cov.: 32

Gnomad AFR AF: 0.816

Gnomad AMI AF: 0.567

Gnomad AMR AF: 0.628

Gnomad ASJ AF: 0.581

Gnomad EAS AF: 0.708

Gnomad SAS AF: 0.414

Gnomad FIN AF: 0.543

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.549

Gnomad OTH AF: 0.603

GnomAD4 exome AF: 0.547 AC: 687281 AN: 1256316 Hom.: 192321 AF XY: 0.540 AC XY: 342013 AN XY: 632976

Gnomad4 AFR exome AF: 0.821

Gnomad4 AMR exome AF: 0.665

Gnomad4 ASJ exome AF: 0.571

Gnomad4 EAS exome AF: 0.636

Gnomad4 SAS exome AF: 0.405

Gnomad4 FIN exome AF: 0.560

Gnomad4 NFE exome AF: 0.540

Gnomad4 OTH exome AF: 0.564

GnomAD4 genome AF: 0.632 AC: 96126 AN: 151992 Hom.: 31459 Cov.: 32 AF XY: 0.627 AC XY: 46581 AN XY: 74272

Gnomad4 AFR AF: 0.816

Gnomad4 AMR AF: 0.628

Gnomad4 ASJ AF: 0.581

Gnomad4 EAS AF: 0.708

Gnomad4 SAS AF: 0.416

Gnomad4 FIN AF: 0.543

Gnomad4 NFE AF: 0.549

Gnomad4 OTH AF: 0.604

Alfa AF: 0.554 Hom.: 3404

Bravo AF: 0.655

Asia WGS AF: 0.581 AC: 2020 AN: 3478

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 19, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	6.3
Dann	Benign	0.77

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: rs7023474; hg19: chr9-21816646; COSMIC: COSV66477127; COSMIC: COSV66477127;