rs12343516

Positions:

• chr9-120841191-A-C
• chr9-120841191-A-G
• chr9-120841191-A-T

Variant summary

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

The NM_005047.4(PSMD5):​c.173+1546T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.471 in 152,162 control chromosomes in the GnomAD database, including 19,979 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 0.47 (19979 hom., cov: 33)
• Consequence: PSMD5 NM_005047.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.37

Genes affected

PSMD5 (HGNC:9563): (proteasome 26S subunit, non-ATPase 5) The 26S proteasome is a multicatalytic proteinase complex with a highly ordered structure composed of 2 complexes, a 20S core and a 19S regulator. The 20S core is composed of 4 rings of 28 non-identical subunits; 2 rings are composed of 7 alpha subunits and 2 rings are composed of 7 beta subunits. The 19S regulator is composed of a base, which contains 6 ATPase subunits and 2 non-ATPase subunits, and a lid, which contains up to 10 non-ATPase subunits. Proteasomes are distributed throughout eukaryotic cells at a high concentration and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway. This gene encodes a non-ATPase subunit of the 19S regulator base that functions as a chaperone protein during 26S proteasome assembly. [provided by RefSeq, Jul 2012]

CUTALP (HGNC:27367): (cutA divalent cation tolerance like, pseudogene)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.716 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSMD5	NM_005047.4	c.173+1546T>G		intron_variant		ENST00000210313.8	NP_005038.1
PSMD5	NM_001270427.2	c.173+1546T>G		intron_variant			NP_001257356.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PSMD5	ENST00000210313.8	c.173+1546T>G		intron_variant		1	NM_005047.4	ENSP00000210313	P1
CUTALP	ENST00000589026.5	n.144-3802A>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.471 AC: 71606 AN: 152044 Hom.: 19968 Cov.: 33

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.396

Gnomad AMR AF: 0.620

Gnomad ASJ AF: 0.651

Gnomad EAS AF: 0.475

Gnomad SAS AF: 0.734

Gnomad FIN AF: 0.587

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.583

Gnomad OTH AF: 0.522

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

GnomAD4 genome AF: 0.471 AC: 71620 AN: 152162 Hom.: 19979 Cov.: 33 AF XY: 0.480 AC XY: 35680 AN XY: 74400

Gnomad4 AFR AF: 0.153

Gnomad4 AMR AF: 0.620

Gnomad4 ASJ AF: 0.651

Gnomad4 EAS AF: 0.475

Gnomad4 SAS AF: 0.736

Gnomad4 FIN AF: 0.587

Gnomad4 NFE AF: 0.583

Gnomad4 OTH AF: 0.523

Alfa AF: 0.405 Hom.: 1720

Bravo AF: 0.457

Asia WGS AF: 0.573 AC: 1994 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.20
DANN	Benign	0.39

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: rs12343516; hg19: chr9-123603469;