18-26166186-C-T

Variant names:

• chr18-26166186-C-T
• rs8095871
• NM_001025096.2:c.477+7942C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001025096.2(PSMA8):​c.477+7942C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 152,010 control chromosomes in the GnomAD database, including 8,937 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 (8937 hom., cov: 32)
• Consequence: PSMA8 NM_001025096.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.185
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.605 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSMA8	NM_001025096.2	c.477+7942C>T		intron_variant	Intron 4 of 6	ENST00000415576.7	NP_001020267.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSMA8	ENST00000415576.7	c.477+7942C>T		intron_variant	Intron 4 of 6	1	NM_001025096.2	ENSP00000409284.2

Frequencies

GnomAD3 genomes AF: 0.257 AC: 39070 AN: 151894 Hom.: 8907 Cov.: 32

Gnomad AFR AF: 0.611

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.230

Gnomad ASJ AF: 0.0896

Gnomad EAS AF: 0.272

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0895

Gnomad OTH AF: 0.219

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

GnomAD4 genome AF: 0.258 AC: 39152 AN: 152010 Hom.: 8937 Cov.: 32 AF XY: 0.255 AC XY: 18917 AN XY: 74298

African (AFR) AF: 0.611 AC: 25295 AN: 41398

American (AMR) AF: 0.230 AC: 3506 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.0896 AC: 311 AN: 3470

East Asian (EAS) AF: 0.272 AC: 1404 AN: 5166

South Asian (SAS) AF: 0.108 AC: 521 AN: 4816

European-Finnish (FIN) AF: 0.136 AC: 1438 AN: 10592

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.0895 AC: 6085 AN: 67990

Other (OTH) AF: 0.218 AC: 461 AN: 2110

Alfa AF: 0.122 Hom.: 1210

Bravo AF: 0.284

Asia WGS AF: 0.227 AC: 788 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	2.3
DANN	Benign	0.25
PhyloP100		0.18
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8095871; hg19: chr18-23746150;