rs9304491

Positions:

• chr18-26138645-T-C

Variant summary

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

The NM_001025096.2(PSMA8):​c.102+4578T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 152,120 control chromosomes in the GnomAD database, including 8,818 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 (8818 hom., cov: 32)
• Consequence: PSMA8 NM_001025096.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.228

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.599 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSMA8	NM_001025096.2	c.102+4578T>C		intron_variant		ENST00000415576.7	NP_001020267.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PSMA8	ENST00000415576.7	c.102+4578T>C		intron_variant		1	NM_001025096.2	ENSP00000409284	P3
PSMA8	ENST00000308268.10	c.102+4578T>C		intron_variant		1		ENSP00000311121	A1
PSMA8	ENST00000343848.10	c.102+4578T>C		intron_variant		1		ENSP00000345584
PSMA8	ENST00000538664.2	c.103-1400T>C		intron_variant, NMD_transcript_variant		1		ENSP00000440327

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38844 AN: 152002 Hom.: 8791 Cov.: 32

Gnomad AFR AF: 0.605

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.0896

Gnomad EAS AF: 0.272

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0894

Gnomad OTH AF: 0.218

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

GnomAD4 genome AF: 0.256 AC: 38922 AN: 152120 Hom.: 8818 Cov.: 32 AF XY: 0.253 AC XY: 18823 AN XY: 74392

Gnomad4 AFR AF: 0.605

Gnomad4 AMR AF: 0.229

Gnomad4 ASJ AF: 0.0896

Gnomad4 EAS AF: 0.272

Gnomad4 SAS AF: 0.107

Gnomad4 FIN AF: 0.136

Gnomad4 NFE AF: 0.0894

Gnomad4 OTH AF: 0.217

Alfa AF: 0.198 Hom.: 978

Bravo AF: 0.282

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	-0.90
CADD	Benign	2.5
DANN	Benign	0.76

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: rs9304491; hg19: chr18-23718609;