chr16-74305672-A-G

Position:

• chr16-74305672-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002811.5(PSMD7):​c.914A>G​(p.Glu305Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: PSMD7 NM_002811.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.04

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]

ENSG00000259972 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13450813).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSMD7	NM_002811.5	c.914A>G	p.Glu305Gly	missense_variant	7/7	ENST00000219313.9	NP_002802.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PSMD7	ENST00000219313.9	c.914A>G	p.Glu305Gly	missense_variant	7/7	1	NM_002811.5	ENSP00000219313.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 17, 2023

The c.914A>G (p.E305G) alteration is located in exon 7 (coding exon 7) of the PSMD7 gene. This alteration results from a A to G substitution at nucleotide position 914, causing the glutamic acid (E) at amino acid position 305 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.024	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.12
Eigen_PC	Benign	0.11
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.36	N
REVEL	Benign	0.13
Sift	Benign	0.21	T
Sift4G	Benign	0.17	T
Polyphen		0.010	B
Vest4		0.32
MutPred		0.21		Gain of loop (P = 0.0097);
MVP		0.60
MPC		0.53
ClinPred		0.72	D
GERP RS		5.0
Varity_R		0.12
gMVP		0.079

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

LitVar

Other links and lift over

dbSNP: rs2034190485; hg19: chr16-74339570;