6-3259143-G-C

Position:

• chr6-3259143-G-C

Variant summary

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

The NM_001128591.2(PSMG4):​c.121G>C​(p.Val41Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PSMG4 NM_001128591.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.83

Genes affected

PSMG4 (HGNC:21108): (proteasome assembly chaperone 4) Predicted to be involved in proteasome 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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSMG4	NM_001128591.2	c.121G>C	p.Val41Leu	missense_variant	1/3	ENST00000438998.7	NP_001122063.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PSMG4	ENST00000438998.7	c.121G>C	p.Val41Leu	missense_variant	1/3	2	NM_001128591.2	ENSP00000413353	P1

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

May 13, 2024

The c.121G>C (p.V41L) alteration is located in exon 1 (coding exon 1) of the PSMG4 gene. This alteration results from a G to C substitution at nucleotide position 121, causing the valine (V) at amino acid position 41 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	Pathogenic	0.93
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.038	T;.;.;.;.
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Benign	0.67	D
LIST_S2	Uncertain	0.88	D;D;D;D;D
M_CAP	Pathogenic	0.71	D
MetaRNN	Uncertain	0.53	D;D;D;D;D
MetaSVM	Benign	-0.44	T
MutationAssessor	Uncertain	2.2	M;.;M;M;.
MutationTaster	Benign	1.0	D;D;D;D;D;D
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	-1.3	N;N;N;N;N
REVEL	Uncertain	0.32
Sift	Benign	0.030	D;T;D;T;T
Sift4G	Uncertain	0.042	D;D;D;D;D
Polyphen		0.99	D;.;.;.;.
Vest4		0.56
MutPred		0.48		Loss of sheet (P = 0.0063);Loss of sheet (P = 0.0063);Loss of sheet (P = 0.0063);Loss of sheet (P = 0.0063);Loss of sheet (P = 0.0063);
MVP		0.030
ClinPred		0.97	D
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9
Varity_R		0.87
gMVP		0.20

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: rs1757866927; hg19: chr6-3259377;