NM_002789.6:c.569T>C

Variant names:

• chr15-78546636-T-C
• NM_002789.6:c.569T>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_002789.6(PSMA4):​c.569T>C​(p.Leu190Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PSMA4 NM_002789.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.79
• Publications: 0 publications found

Genes affected

PSMA4 (HGNC:9533): (proteasome 20S subunit alpha 4) This gene encodes a core alpha subunit of the 20S proteosome, which is a highly ordered ring-shaped structure composed of four rings of 28 non-identical subunits. Proteasomes cleave peptides in an ATP- and ubiquitin-dependent manner. [provided by RefSeq, Aug 2016]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.93

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002789.6. 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
	PSMA4	NM_002789.6	MANE Select	c.569T>C	p.Leu190Pro	missense	Exon 8 of 9	NP_002780.1	P25789-1
	PSMA4	NM_001102667.2		c.569T>C	p.Leu190Pro	missense	Exon 8 of 9	NP_001096137.1	P25789-1
	PSMA4	NM_001330676.2		c.569T>C	p.Leu190Pro	missense	Exon 8 of 9	NP_001317605.1	P25789-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSMA4	ENST00000044462.12	TSL:1 MANE Select	c.569T>C	p.Leu190Pro	missense	Exon 8 of 9	ENSP00000044462.7	P25789-1
	PSMA4	ENST00000413382.6	TSL:1	c.356T>C	p.Leu119Pro	missense	Exon 7 of 8	ENSP00000402118.2	P25789-2
	PSMA4	ENST00000559934.5	TSL:1	n.2562T>C		non_coding_transcript_exon	Exon 5 of 6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.14
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.39	T
Eigen	Pathogenic	0.80
Eigen_PC	Pathogenic	0.80
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.97	D
M_CAP	Benign	0.051	D
MetaRNN	Pathogenic	0.93	D
MetaSVM	Benign	-0.90	T
MutationAssessor	Pathogenic	2.9	M
PhyloP100		7.8
PrimateAI	Pathogenic	0.86	D
PROVEAN	Uncertain	-3.0	D
REVEL	Uncertain	0.53
Sift	Benign	0.073	T
Sift4G	Benign	0.099	T
Polyphen		0.99	D
Vest4		0.90
MutPred		0.84		Gain of disorder (P = 0.0397)
MVP		0.67
MPC		1.0
ClinPred		0.97	D
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.87
gMVP		0.98

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

hg19: chr15-78838978;