rs191447831

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr7-1569329-G-A
• chr7-1569329-G-T

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>T​(p.Thr4Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000056 in 1,605,964 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: PSMG3 NM_032302.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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=0.022946596).

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>T	p.Thr4Met	missense	Exon 1 of 2	NP_115678.1	Q9BT73
	PSMG3	NM_001134340.2		c.11C>T	p.Thr4Met	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>T	p.Thr4Met	missense	Exon 1 of 2	ENSP00000288607.2	Q9BT73
	PSMG3	ENST00000252329.3	TSL:3	c.11C>T	p.Thr4Met	missense	Exon 2 of 3	ENSP00000252329.3	Q9BT73
	PSMG3	ENST00000404674.7	TSL:2	c.11C>T	p.Thr4Met	missense	Exon 2 of 3	ENSP00000384799.3	Q9BT73

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152218 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000829 AC: 2 AN: 241188 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000185

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000413 AC: 6 AN: 1453628 Hom.: 0 Cov.: 31 AF XY: 0.00000415 AC XY: 3 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: 0.0000117 AC: 1 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: 0.00000361 AC: 4 AN: 1108376

Other (OTH) AF: 0.0000167 AC: 1 AN: 59976

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152336 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74504

African (AFR) AF: 0.00 AC: 0 AN: 41574

American (AMR) AF: 0.0000653 AC: 1 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	6.5
DANN	Benign	0.81
DEOGEN2	Benign	0.024	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.045	N
LIST_S2	Benign	0.30	T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.023	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.13
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.040
Sift	Benign	0.090	T
Sift4G	Benign	0.10	T
Polyphen		0.020	B
Vest4		0.074
MVP		0.040
MPC		0.40
ClinPred		0.059	T
GERP RS		-5.7
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0
Varity_R		0.041
gMVP		0.32
Mutation Taster		=99/1	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;