16-74305672-A-C

Variant names:

• chr16-74305672-A-C
• rs2034190485
• NM_002811.5:c.914A>C

Variant summary

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

The NM_002811.5(PSMD7):​c.914A>C​(p.Glu305Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000731 in 1,367,338 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E305G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: PSMD7 NM_002811.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.04
• Publications: 0 publications found

Genes affected

PSMD7 (HGNC:9565): (proteasome 26S subunit, non-ATPase 7) 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. An essential function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides. This gene encodes a non-ATPase subunit of the 19S regulator. A pseudogene has been identified on chromosome 17. [provided by RefSeq, Jul 2008]

PDPR2P (HGNC:):

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=0.13656121).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002811.5. 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
	PSMD7	NM_002811.5	MANE Select	c.914A>C	p.Glu305Ala	missense	Exon 7 of 7	NP_002802.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSMD7	ENST00000219313.9	TSL:1 MANE Select	c.914A>C	p.Glu305Ala	missense	Exon 7 of 7	ENSP00000219313.4	P51665
	PSMD7	ENST00000937729.1		c.821A>C	p.Glu274Ala	missense	Exon 6 of 6	ENSP00000607788.1
	PSMD7	ENST00000937730.1		c.803A>C	p.Glu268Ala	missense	Exon 7 of 7	ENSP00000607789.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.31e-7 AC: 1 AN: 1367338 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 669246

African (AFR) AF: 0.00 AC: 0 AN: 30444

American (AMR) AF: 0.00 AC: 0 AN: 30616

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20804

East Asian (EAS) AF: 0.0000259 AC: 1 AN: 38622

South Asian (SAS) AF: 0.00 AC: 0 AN: 70690

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50210

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5336

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1064332

Other (OTH) AF: 0.00 AC: 0 AN: 56284

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.044	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.12
Eigen_PC	Benign	0.097
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.4	L
PhyloP100		9.0
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-0.73	N
REVEL	Benign	0.11
Sift	Benign	0.36	T
Sift4G	Benign	0.38	T
Polyphen		0.010	B
Vest4		0.37
MutPred		0.19		Gain of MoRF binding (P = 0.014)
MVP		0.60
MPC		0.48
ClinPred		0.79	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.8
Varity_R		0.15
gMVP		0.11

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: rs2034190485; hg19: chr16-74339570;