7-1569329-G-T

Variant names:

• chr7-1569329-G-T
• rs191447831
• NM_032302.4:c.11C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032302.4(PSMG3):​c.11C>A​(p.Thr4Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,453,628 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T4M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: PSMG3 NM_032302.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.127
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.018035442).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032302.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSMG3	NM_032302.4	MANE Select	c.11C>A	p.Thr4Lys	missense	Exon 1 of 2	NP_115678.1	Q9BT73
	PSMG3	NM_001134340.2		c.11C>A	p.Thr4Lys	missense	Exon 2 of 3	NP_001127812.1	Q9BT73

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSMG3	ENST00000288607.3	TSL:1 MANE Select	c.11C>A	p.Thr4Lys	missense	Exon 1 of 2	ENSP00000288607.2	Q9BT73
	PSMG3	ENST00000252329.3	TSL:3	c.11C>A	p.Thr4Lys	missense	Exon 2 of 3	ENSP00000252329.3	Q9BT73
	PSMG3	ENST00000404674.7	TSL:2	c.11C>A	p.Thr4Lys	missense	Exon 2 of 3	ENSP00000384799.3	Q9BT73

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1453628 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 722534

African (AFR) AF: 0.00 AC: 0 AN: 33262

American (AMR) AF: 0.00 AC: 0 AN: 44118

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25998

East Asian (EAS) AF: 0.00 AC: 0 AN: 39366

South Asian (SAS) AF: 0.00 AC: 0 AN: 85592

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52492

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4448

European-Non Finnish (NFE) AF: 9.02e-7 AC: 1 AN: 1108376

Other (OTH) AF: 0.00 AC: 0 AN: 59976

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.044
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.023
DANN	Benign	0.57
DEOGEN2	Benign	0.0058	T
Eigen	Benign	-2.0
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.0075	N
LIST_S2	Benign	0.20	T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.018	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.8	N
PhyloP100		-0.13
PrimateAI	Benign	0.30	T
PROVEAN	Benign	0.0	N
REVEL	Benign	0.0070
Sift	Benign	1.0	T
Sift4G	Benign	0.94	T
Polyphen		0.0	B
Vest4		0.082
MutPred		0.19		Gain of ubiquitination at T4 (P = 0.0066)
MVP		0.048
MPC		0.47
ClinPred		0.060	T
GERP RS		-5.7
Varity_R		0.12
gMVP		0.29
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs191447831; hg19: chr7-1608965;