rs12482181

Positions:

• chr21-39176926-A-G

Variant summary

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

The NM_003720.4(PSMG1):​c.792+509T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 152,114 control chromosomes in the GnomAD database, including 7,408 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 0.30 (7408 hom., cov: 33)
• Consequence: PSMG1 NM_003720.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.524

Genes affected

PSMG1 (HGNC:3043): (proteasome assembly chaperone 1) Enables molecular adaptor activity. Involved in chaperone-mediated protein complex assembly. Located in several cellular components, including Golgi apparatus; endoplasmic reticulum; and nucleoplasm. Part of chaperone complex. [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 (NFE) allele frequency at 95% confidence interval = 0.349 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSMG1	NM_003720.4	c.792+509T>C		intron_variant		ENST00000331573.8	NP_003711.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PSMG1	ENST00000331573.8	c.792+509T>C		intron_variant		1	NM_003720.4	ENSP00000329915	P1

Frequencies

GnomAD3 genomes AF: 0.303 AC: 45991 AN: 151996 Hom.: 7409 Cov.: 33

Gnomad AFR AF: 0.299

Gnomad AMI AF: 0.460

Gnomad AMR AF: 0.262

Gnomad ASJ AF: 0.342

Gnomad EAS AF: 0.0352

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.209

Gnomad MID AF: 0.344

Gnomad NFE AF: 0.352

Gnomad OTH AF: 0.297

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

GnomAD4 genome AF: 0.302 AC: 45997 AN: 152114 Hom.: 7408 Cov.: 33 AF XY: 0.291 AC XY: 21674 AN XY: 74356

Gnomad4 AFR AF: 0.298

Gnomad4 AMR AF: 0.261

Gnomad4 ASJ AF: 0.342

Gnomad4 EAS AF: 0.0352

Gnomad4 SAS AF: 0.197

Gnomad4 FIN AF: 0.209

Gnomad4 NFE AF: 0.352

Gnomad4 OTH AF: 0.298

Alfa AF: 0.330 Hom.: 4197

Bravo AF: 0.307

Asia WGS AF: 0.140 AC: 489 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	7.5
DANN	Benign	0.69

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: rs12482181; hg19: chr21-40548852;