chr15-78546641-T-G

Position:

• chr15-78546641-T-G

Variant summary

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

The NM_002789.6(PSMA4):​c.574T>G​(p.Leu192Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 0.296

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSMA4	NM_002789.6	c.574T>G	p.Leu192Val	missense_variant	8/9	ENST00000044462.12	NP_002780.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PSMA4	ENST00000044462.12	c.574T>G	p.Leu192Val	missense_variant	8/9	1	NM_002789.6	ENSP00000044462	P1

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 28, 2023

The c.574T>G (p.L192V) alteration is located in exon 8 (coding exon 7) of the PSMA4 gene. This alteration results from a T to G substitution at nucleotide position 574, causing the leucine (L) at amino acid position 192 to be replaced by a valine (V). 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	Benign	0.23
BayesDel_addAF	Uncertain	0.055	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.29	.;T;T;.;.;.;T;T;.;T
Eigen	Uncertain	0.26
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Pathogenic	0.99	D;.;D;D;D;D;D;D;D;D
M_CAP	Benign	0.037	D
MetaRNN	Uncertain	0.59	D;D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.6	.;M;M;.;.;.;.;.;.;.
MutationTaster	Benign	1.0	D;D;D;D;D;D;D
PrimateAI	Uncertain	0.77	T
PROVEAN	Uncertain	-2.6	D;D;D;D;D;D;D;D;D;D
REVEL	Uncertain	0.31
Sift	Uncertain	0.0080	D;T;T;T;D;T;T;T;T;T
Sift4G	Benign	0.077	T;T;T;T;T;T;T;T;T;T
Polyphen		1.0	.;D;D;.;.;.;.;.;.;.
Vest4		0.70
MutPred		0.68		.;Gain of methylation at K187 (P = 0.0746);Gain of methylation at K187 (P = 0.0746);.;.;.;Gain of methylation at K187 (P = 0.0746);Gain of methylation at K187 (P = 0.0746);Gain of methylation at K187 (P = 0.0746);.;
MVP		0.56
MPC		0.60
ClinPred		0.97	D
GERP RS		0.88
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.44
gMVP		0.79

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: chr15-78838983;