6-3263706-C-T

Position:

• chr6-3263706-C-T

Variant summary

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

The NM_001128591.2(PSMG4):​c.197C>T​(p.Ser66Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 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: 1.55

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2505989).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PSMG4	NM_001128591.2	c.197C>T	p.Ser66Phe	missense_variant	2/3	ENST00000438998.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSMG4	ENST00000438998.7	c.197C>T	p.Ser66Phe	missense_variant	2/3	2	NM_001128591.2	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

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

Nov 05, 2021

The c.197C>T (p.S66F) alteration is located in exon 2 (coding exon 2) of the PSMG4 gene. This alteration results from a C to T substitution at nucleotide position 197, causing the serine (S) at amino acid position 66 to be replaced by a phenylalanine (F). 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	0.47
BayesDel_addAF	Benign	0.0091	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T;.;.
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Benign	0.74	D
LIST_S2	Uncertain	0.88	D;D;D
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.25	T;T;T
MetaSVM	Benign	-0.74	T
MutationAssessor	Uncertain	2.1	M;M;M
MutationTaster	Benign	1.0	D;D;D;N;N;N
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-3.0	D;D;D
REVEL	Benign	0.14
Sift	Benign	0.13	T;D;D
Sift4G	Benign	0.27	T;T;T
Polyphen		0.34	B;.;.
Vest4		0.34
MutPred		0.36		Loss of disorder (P = 8e-04);Loss of disorder (P = 8e-04);Loss of disorder (P = 8e-04);
MVP		0.081
ClinPred		0.90	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.61
gMVP		0.31

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: rs1300474129; hg19: chr6-3263940;