rs4065321

Positions:

• chr17-39987295-C-T

Variant summary

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

The NM_002809.4(PSMD3):​c.549+583C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.561 in 152,020 control chromosomes in the GnomAD database, including 24,199 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 0.56 (24199 hom., cov: 32)
• Consequence: PSMD3 NM_002809.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.507

Genes affected

PSMD3 (HGNC:9560): (proteasome 26S subunit, non-ATPase 3) 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 member of the proteasome subunit S3 family that functions as one of the non-ATPase subunits of the 19S regulator lid. Single nucleotide polymorphisms in this gene are associated with neutrophil count. [provided by RefSeq, Jul 2012]

LOC124904000 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSMD3	NM_002809.4	c.549+583C>T		intron_variant		ENST00000264639.9	NP_002800.2
LOC124904000	XR_007065751.1	n.3658-513G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PSMD3	ENST00000264639.9	c.549+583C>T		intron_variant		1	NM_002809.4	ENSP00000264639	P1
PSMD3	ENST00000540504.2	c.104+583C>T		intron_variant		3		ENSP00000444980
PSMD3	ENST00000415039.7	c.*23+583C>T		intron_variant, NMD_transcript_variant		2		ENSP00000407410
PSMD3	ENST00000580980.1	n.29+583C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.561 AC: 85265 AN: 151902 Hom.: 24190 Cov.: 32

Gnomad AFR AF: 0.639

Gnomad AMI AF: 0.440

Gnomad AMR AF: 0.568

Gnomad ASJ AF: 0.554

Gnomad EAS AF: 0.420

Gnomad SAS AF: 0.543

Gnomad FIN AF: 0.471

Gnomad MID AF: 0.747

Gnomad NFE AF: 0.539

Gnomad OTH AF: 0.590

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

GnomAD4 genome AF: 0.561 AC: 85316 AN: 152020 Hom.: 24199 Cov.: 32 AF XY: 0.556 AC XY: 41329 AN XY: 74274

Gnomad4 AFR AF: 0.639

Gnomad4 AMR AF: 0.567

Gnomad4 ASJ AF: 0.554

Gnomad4 EAS AF: 0.420

Gnomad4 SAS AF: 0.542

Gnomad4 FIN AF: 0.471

Gnomad4 NFE AF: 0.539

Gnomad4 OTH AF: 0.588

Alfa AF: 0.551 Hom.: 46725

Bravo AF: 0.575

Asia WGS AF: 0.505 AC: 1762 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.8
DANN	Benign	0.75

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: rs4065321; hg19: chr17-38143548;