rs4800723

chr18-26175194-T-Cchr18-26175194-T-G

Variant summary

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

The NM_001025096.2(PSMA8):c.478-3636T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 152,076 control chromosomes in the GnomAD database, including 9,083 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 0.26 (9083 hom., cov: 32)
• Consequence: PSMA8 NM_001025096.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.281

Genes affected

PSMA8 (HGNC:22985): (proteasome 20S subunit alpha 8) Predicted to be involved in meiotic cell cycle and proteasomal protein catabolic process. Located in extracellular exosome and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.61 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PSMA8	NM_001025096.2	c.478-3636T>C		intron_variant		ENST00000415576.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSMA8	ENST00000415576.7	c.478-3636T>C		intron_variant		1	NM_001025096.2	P3

Frequencies

GnomAD3 genomes AF: 0.259 AC: 39285 AN: 151958 Hom.: 9050 Cov.: 32

Gnomad AFR AF: 0.615

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.230

Gnomad ASJ AF: 0.0896

Gnomad EAS AF: 0.273

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.115

Gnomad NFE AF: 0.0895

Gnomad OTH AF: 0.220

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

GnomAD4 genome AF: 0.259 AC: 39370 AN: 152076 Hom.: 9083 Cov.: 32 AF XY: 0.256 AC XY: 19041 AN XY: 74372

Gnomad4 AFR AF: 0.616

Gnomad4 AMR AF: 0.230

Gnomad4 ASJ AF: 0.0896

Gnomad4 EAS AF: 0.273

Gnomad4 SAS AF: 0.108

Gnomad4 FIN AF: 0.135

Gnomad4 NFE AF: 0.0894

Gnomad4 OTH AF: 0.219

Alfa AF: 0.0995 Hom.: 658

Bravo AF: 0.286

Asia WGS AF: 0.229 AC: 793 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.74
Dann	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4800723; hg19: chr18-23755158;