rs1007310917

Variant names:

• chr17-39981000-C-T
• rs1007310917
• NM_002809.4:c.30C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_002809.4(PSMD3):​c.30C>T​(p.Arg10Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000932 in 1,395,324 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000093 (0 hom.)
• Consequence: PSMD3 NM_002809.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.450
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.24).
• BP6: Variant 17-39981000-C-T is Benign according to our data. Variant chr17-39981000-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2647731.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.45 with no splicing effect.
• BS2: High AC in GnomAdExome4 at 13 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002809.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSMD3	NM_002809.4	MANE Select	c.30C>T	p.Arg10Arg	synonymous	Exon 1 of 12	NP_002800.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSMD3	ENST00000264639.9	TSL:1 MANE Select	c.30C>T	p.Arg10Arg	synonymous	Exon 1 of 12	ENSP00000264639.4	O43242-1
	PSMD3	ENST00000916285.1		c.30C>T	p.Arg10Arg	synonymous	Exon 1 of 12	ENSP00000586344.1
	PSMD3	ENST00000916290.1		c.30C>T	p.Arg10Arg	synonymous	Exon 1 of 12	ENSP00000586349.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000932 AC: 13 AN: 1395324 Hom.: 0 Cov.: 30 AF XY: 0.00000436 AC XY: 3 AN XY: 688242

African (AFR) AF: 0.00 AC: 0 AN: 31632

American (AMR) AF: 0.00 AC: 0 AN: 34866

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24872

East Asian (EAS) AF: 0.00 AC: 0 AN: 36276

South Asian (SAS) AF: 0.00 AC: 0 AN: 79070

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47424

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4588

European-Non Finnish (NFE) AF: 0.0000111 AC: 12 AN: 1078878

Other (OTH) AF: 0.0000173 AC: 1 AN: 57718

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.24
CADD	Benign	13
DANN	Benign	0.95
PhyloP100		0.45
PromoterAI		0.0010	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.9

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

Other links and lift over

dbSNP: rs1007310917; hg19: chr17-38137253;