17-39984352-C-A

Variant names:

• chr17-39984352-C-A
• NM_002809.4:c.279C>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002809.4(PSMD3):​c.279C>A​(p.Phe93Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,534 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PSMD3 NM_002809.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.57

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSMD3	NM_002809.4	c.279C>A	p.Phe93Leu	missense_variant	Exon 2 of 12	ENST00000264639.9	NP_002800.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSMD3	ENST00000264639.9	c.279C>A	p.Phe93Leu	missense_variant	Exon 2 of 12	1	NM_002809.4	ENSP00000264639.4
PSMD3	ENST00000415039.7	n.121-107C>A		intron_variant	Intron 1 of 12	2		ENSP00000407410.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461534 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727064

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Uncertain	0.098	D
BayesDel_noAF	Benign	-0.10
CADD	Benign	4.2
DANN	Benign	0.95
DEOGEN2	Uncertain	0.43	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.44	N
LIST_S2	Uncertain	0.94	D
M_CAP	Uncertain	0.13	D
MetaRNN	Uncertain	0.59	D
MetaSVM	Benign	-0.75	T
MutationAssessor	Uncertain	2.5	M
PrimateAI	Pathogenic	0.88	D
PROVEAN	Pathogenic	-4.6	D
REVEL	Uncertain	0.48
Sift	Benign	0.059	T
Sift4G	Benign	0.26	T
Polyphen		0.012	B
Vest4		0.68
MutPred		0.61		Gain of disorder (P = 0.0796);
MVP		0.88
MPC		0.75
ClinPred		0.93	D
GERP RS		-5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.50
gMVP		0.59

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-38140605;