7-1569248-T-G

Variant names:

• chr7-1569248-T-G
• NM_032302.4:c.92A>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_032302.4(PSMG3):​c.92A>C​(p.His31Pro) variant causes a missense change. 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: 32)
• Consequence: PSMG3 NM_032302.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.60

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37936532).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSMG3	NM_032302.4	c.92A>C	p.His31Pro	missense_variant	Exon 1 of 2	ENST00000288607.3	NP_115678.1
PSMG3	NM_001134340.2	c.92A>C	p.His31Pro	missense_variant	Exon 2 of 3		NP_001127812.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSMG3	ENST00000288607.3	c.92A>C	p.His31Pro	missense_variant	Exon 1 of 2	1	NM_032302.4	ENSP00000288607.2
PSMG3	ENST00000252329.3	c.92A>C	p.His31Pro	missense_variant	Exon 2 of 3	3		ENSP00000252329.3
PSMG3	ENST00000404674.7	c.92A>C	p.His31Pro	missense_variant	Exon 2 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

Dec 07, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.92A>C (p.H31P) alteration is located in exon 1 (coding exon 1) of the PSMG3 gene. This alteration results from a A to C substitution at nucleotide position 92, causing the histidine (H) at amino acid position 31 to be replaced by a proline (P). 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	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.20	T;T;T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.84	.;.;T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.38	T;T;T
MetaSVM	Benign	-0.84	T
MutationAssessor	Uncertain	2.2	M;M;M
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-3.7	D;D;D
REVEL	Benign	0.13
Sift	Benign	0.049	D;D;D
Sift4G	Benign	0.079	T;T;T
Polyphen		0.88	P;P;P
Vest4		0.53
MutPred		0.45		Loss of sheet (P = 0.0104);Loss of sheet (P = 0.0104);Loss of sheet (P = 0.0104);
MVP		0.34
MPC		1.3
ClinPred		0.99	D
GERP RS		5.4
Varity_R		0.94
gMVP		0.85

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: chr7-1608884;