17-39980987-C-T

Variant names:

• chr17-39980987-C-T
• NM_002809.4:c.17C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002809.4(PSMD3):​c.17C>T​(p.Ser6Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000717 in 1,394,054 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: PSMD3 NM_002809.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.87
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12220302).

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.17C>T	p.Ser6Leu	missense	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.17C>T	p.Ser6Leu	missense	Exon 1 of 12	ENSP00000264639.4	O43242-1
	PSMD3	ENST00000916285.1		c.17C>T	p.Ser6Leu	missense	Exon 1 of 12	ENSP00000586344.1
	PSMD3	ENST00000916290.1		c.17C>T	p.Ser6Leu	missense	Exon 1 of 12	ENSP00000586349.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.17e-7 AC: 1 AN: 1394054 Hom.: 0 Cov.: 30 AF XY: 0.00000145 AC XY: 1 AN XY: 687710

African (AFR) AF: 0.00 AC: 0 AN: 31724

American (AMR) AF: 0.00 AC: 0 AN: 34474

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24554

East Asian (EAS) AF: 0.00 AC: 0 AN: 36684

South Asian (SAS) AF: 0.00 AC: 0 AN: 78566

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46954

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4398

European-Non Finnish (NFE) AF: 9.27e-7 AC: 1 AN: 1079050

Other (OTH) AF: 0.00 AC: 0 AN: 57650

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.071	T
BayesDel_noAF	Benign	-0.34
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.086	T
Eigen	Benign	-0.14
Eigen_PC	Benign	0.070
FATHMM_MKL	Benign	0.19	N
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		3.9
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.48	N
REVEL	Benign	0.018
Sift	Uncertain	0.020	D
Sift4G	Benign	0.11	T
Polyphen		0.17	B
Vest4		0.18
MutPred		0.25		Loss of phosphorylation at S6 (P = 0.0018)
MVP		0.18
MPC		0.57
ClinPred		0.88	D
GERP RS		5.0
PromoterAI		0.020	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.29
gMVP		0.41

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

hg19: chr17-38137240;