10-15860304-A-G

Position:

• chr10-15860304-A-G

Variant summary

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

The NM_024948.4(MINDY3):​c.-5T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 1,591,298 control chromosomes in the GnomAD database, including 63,952 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 0.33 (9030 hom., cov: 33)
  • Exomes 𝑓: 0.27 (54922 hom.)
• Consequence: MINDY3 NM_024948.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.18

Genes affected

MINDY3 (HGNC:23578): (MINDY lysine 48 deubiquitinase 3) The protein encoded by this gene contains a caspase-associated recruitment domain and may function in apoptosis. It has been identified as a tumor suppressor in lung and gastric cancers, and a polymorphism in the gene may be associated with gastric cancer risk. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Dec 2015]

MINDY3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.454 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MINDY3	NM_024948.4	c.-5T>C		5_prime_UTR_variant	1/15	ENST00000277632.8	NP_079224.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MINDY3	ENST00000277632.8	c.-5T>C		5_prime_UTR_variant	1/15	1	NM_024948.4	ENSP00000277632.3
MINDY3	ENST00000477891.1	n.195T>C		non_coding_transcript_exon_variant	1/14	1

Frequencies

GnomAD3 genomes AF: 0.333 AC: 50690 AN: 152042 Hom.: 9003 Cov.: 33

Gnomad AFR AF: 0.459

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.275

Gnomad EAS AF: 0.189

Gnomad SAS AF: 0.277

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.305

GnomAD3 exomes AF: 0.293 AC: 63916 AN: 218046 Hom.: 9647 AF XY: 0.292 AC XY: 34208 AN XY: 117042

Gnomad AFR exome AF: 0.455

Gnomad AMR exome AF: 0.297

Gnomad ASJ exome AF: 0.280

Gnomad EAS exome AF: 0.191

Gnomad SAS exome AF: 0.293

Gnomad FIN exome AF: 0.361

Gnomad NFE exome AF: 0.275

Gnomad OTH exome AF: 0.282

GnomAD4 exome AF: 0.272 AC: 391299 AN: 1439138 Hom.: 54922 Cov.: 31 AF XY: 0.272 AC XY: 194461 AN XY: 713892

Gnomad4 AFR exome AF: 0.466

Gnomad4 AMR exome AF: 0.293

Gnomad4 ASJ exome AF: 0.277

Gnomad4 EAS exome AF: 0.191

Gnomad4 SAS exome AF: 0.295

Gnomad4 FIN exome AF: 0.364

Gnomad4 NFE exome AF: 0.261

Gnomad4 OTH exome AF: 0.279

GnomAD4 genome AF: 0.334 AC: 50755 AN: 152160 Hom.: 9030 Cov.: 33 AF XY: 0.338 AC XY: 25107 AN XY: 74388

Gnomad4 AFR AF: 0.460

Gnomad4 AMR AF: 0.317

Gnomad4 ASJ AF: 0.275

Gnomad4 EAS AF: 0.188

Gnomad4 SAS AF: 0.277

Gnomad4 FIN AF: 0.371

Gnomad4 NFE AF: 0.275

Gnomad4 OTH AF: 0.303

Alfa AF: 0.300 Hom.: 6262

Bravo AF: 0.336

Asia WGS AF: 0.246 AC: 853 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	16
DANN	Benign	0.72

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: rs2297882; hg19: chr10-15902303; COSMIC: COSV53220020;