rs4800723

Variant names:

• chr18-26175194-T-C
• rs4800723
• NM_001025096.2:c.478-3636T>C

Your query was ambiguous. Multiple possible variants found:

• chr18-26175194-T-C
• chr18-26175194-T-G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.61 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001025096.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSMA8	NM_001025096.2	MANE Select	c.478-3636T>C		intron	N/A	NP_001020267.1
	PSMA8	NM_144662.3		c.496-3636T>C		intron	N/A	NP_653263.2
	PSMA8	NM_001308188.2		c.400-3636T>C		intron	N/A	NP_001295117.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSMA8	ENST00000415576.7	TSL:1 MANE Select	c.478-3636T>C		intron	N/A	ENSP00000409284.2
	PSMA8	ENST00000308268.10	TSL:1	c.496-3636T>C		intron	N/A	ENSP00000311121.6
	PSMA8	ENST00000343848.10	TSL:1	c.364-3636T>C		intron	N/A	ENSP00000345584.6

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

African (AFR) AF: 0.616 AC: 25501 AN: 41406

American (AMR) AF: 0.230 AC: 3511 AN: 15278

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

East Asian (EAS) AF: 0.273 AC: 1416 AN: 5182

South Asian (SAS) AF: 0.108 AC: 521 AN: 4826

European-Finnish (FIN) AF: 0.135 AC: 1433 AN: 10582

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 292

European-Non Finnish (NFE) AF: 0.0894 AC: 6084 AN: 68018

Other (OTH) AF: 0.219 AC: 462 AN: 2110

Alfa AF: 0.100 Hom.: 732

Bravo AF: 0.286

Asia WGS AF: 0.229 AC: 793 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.74
DANN	Benign	0.67
PhyloP100		-0.28
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4800723; hg19: chr18-23755158;