9-21930148-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000580900.5(MTAP):c.814-860G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 401,890 control chromosomes in the GnomAD database, including 27,988 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 0.38 (14891 hom., cov: 33)
  • Exomes 𝑓: 0.29 (13097 hom.)
• Consequence: MTAP ENST00000580900.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.671

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]

ERVFRD-3 (HGNC:49792): (endogenous retrovirus group FRD member 3)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.706 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTAP	NM_001396041.1	c.814-860G>C		intron_variant
MTAP	NM_001396042.1	c.691-9012G>C		intron_variant
MTAP	NM_001396043.1	c.814-9012G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTAP	ENST00000577563.1	c.148-860G>C		intron_variant		1
MTAP	ENST00000580900.5	c.814-860G>C		intron_variant		1
ERVFRD-3	ENST00000578561.1	n.692G>C		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.383 AC: 58189 AN: 151946 Hom.: 14843 Cov.: 33

Gnomad AFR AF: 0.713

Gnomad AMI AF: 0.358

Gnomad AMR AF: 0.410

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.498

Gnomad SAS AF: 0.334

Gnomad FIN AF: 0.267

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.198

Gnomad OTH AF: 0.346

GnomAD4 exome AF: 0.290 AC: 72375 AN: 249826 Hom.: 13097 Cov.: 0 AF XY: 0.284 AC XY: 40862 AN XY: 143730

Gnomad4 AFR exome AF: 0.722

Gnomad4 AMR exome AF: 0.532

Gnomad4 ASJ exome AF: 0.254

Gnomad4 EAS exome AF: 0.510

Gnomad4 SAS exome AF: 0.329

Gnomad4 FIN exome AF: 0.275

Gnomad4 NFE exome AF: 0.205

Gnomad4 OTH exome AF: 0.285

GnomAD4 genome AF: 0.383 AC: 58305 AN: 152064 Hom.: 14891 Cov.: 33 AF XY: 0.386 AC XY: 28689 AN XY: 74334

Gnomad4 AFR AF: 0.713

Gnomad4 AMR AF: 0.411

Gnomad4 ASJ AF: 0.235

Gnomad4 EAS AF: 0.498

Gnomad4 SAS AF: 0.334

Gnomad4 FIN AF: 0.267

Gnomad4 NFE AF: 0.198

Gnomad4 OTH AF: 0.348

Alfa AF: 0.176 Hom.: 409

Bravo AF: 0.413

Asia WGS AF: 0.437 AC: 1520 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.51
Dann	Benign	0.61

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: rs7864029; hg19: chr9-21930147;