7-1567811-C-A

Variant names:

• chr7-1567811-C-A
• NM_032302.4:c.256G>T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_032302.4(PSMG3):​c.256G>T​(p.Val86Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PSMG3 NM_032302.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.10

Genes affected

PSMG3 (HGNC:22420): (proteasome assembly chaperone 3) Enables molecular adaptor activity. Involved in chaperone-mediated protein complex assembly. Predicted to be part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.756

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSMG3	NM_032302.4	c.256G>T	p.Val86Leu	missense_variant	Exon 2 of 2	ENST00000288607.3	NP_115678.1
PSMG3	NM_001134340.2	c.256G>T	p.Val86Leu	missense_variant	Exon 3 of 3		NP_001127812.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSMG3	ENST00000288607.3	c.256G>T	p.Val86Leu	missense_variant	Exon 2 of 2	1	NM_032302.4	ENSP00000288607.2
PSMG3	ENST00000252329.3	c.256G>T	p.Val86Leu	missense_variant	Exon 3 of 3	3		ENSP00000252329.3
PSMG3	ENST00000404674.7	c.256G>T	p.Val86Leu	missense_variant	Exon 3 of 3	2		ENSP00000384799.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 09, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.256G>T (p.V86L) alteration is located in exon 2 (coding exon 2) of the PSMG3 gene. This alteration results from a G to T substitution at nucleotide position 256, causing the valine (V) at amino acid position 86 to be replaced by a leucine (L). 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	Uncertain	0.55
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.26
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.041	T;T;T
Eigen	Pathogenic	0.88
Eigen_PC	Pathogenic	0.85
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.90	.;.;D
M_CAP	Benign	0.016	T
MetaRNN	Pathogenic	0.76	D;D;D
MetaSVM	Uncertain	0.060	D
MutationAssessor	Uncertain	2.8	M;M;M
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-1.3	N;N;N
REVEL	Uncertain	0.29
Sift	Uncertain	0.024	D;D;D
Sift4G	Uncertain	0.040	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.81
MutPred		0.63		Loss of sheet (P = 0.0142);Loss of sheet (P = 0.0142);Loss of sheet (P = 0.0142);
MVP		0.45
MPC		0.96
ClinPred		0.96	D
GERP RS		5.7
Varity_R		0.61
gMVP		0.68

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: chr7-1607447;