rs8053

Positions:

• chr15-78548878-T-A
• chr15-78548878-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002789.6(PSMA4):​c.720T>A​(p.His240Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PSMA4 NM_002789.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.576

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21109915).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PSMA4	NM_002789.6	c.720T>A	p.His240Gln	missense_variant	9/9	ENST00000044462.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSMA4	ENST00000044462.12	c.720T>A	p.His240Gln	missense_variant	9/9	1	NM_002789.6	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1460448 Hom.: 0 Cov.: 49 AF XY: 0.00 AC XY: 0 AN XY: 726446

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	0.14
DANN	Benign	0.39
DEOGEN2	Benign	0.26	.;T;T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.34	N
LIST_S2	Benign	0.80	T;.;T;T
MetaRNN	Benign	0.21	T;T;T;T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	1.8	.;L;L;.
MutationTaster	Benign	1.0	P;P;P;P;P;P;P
PrimateAI	Pathogenic	0.83	D
PROVEAN	Uncertain	-2.5	D;D;D;N
REVEL	Benign	0.28
Sift	Benign	0.22	T;T;T;T
Sift4G	Benign	0.28	T;T;T;T
Polyphen		0.85	.;P;P;.
Vest4		0.56
MutPred		0.27		.;Gain of helix (P = 0.0425);Gain of helix (P = 0.0425);.;
MVP		0.56
MPC		0.28
ClinPred		0.77	D
GERP RS		-7.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.8
Varity_R		0.25
gMVP		0.44

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

LitVar

Other links and lift over

dbSNP: rs8053; hg19: chr15-78841220;