rs2302878

Positions:

• chr2-53908799-T-A
• chr2-53908799-T-C

Variant summary

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

The ENST00000404125.6(PSME4):​c.2614A>T​(p.Ile872Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 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. I872V) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PSME4 ENST00000404125.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.86

Genes affected

PSME4 (HGNC:20635): (proteasome activator subunit 4) Predicted to enable lysine-acetylated histone binding activity; peptidase activator activity; and proteasome binding activity. Predicted to be involved in DNA repair; proteasomal ubiquitin-independent protein catabolic process; and spermatogenesis, exchange of chromosomal proteins. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

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=0.15176725).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSME4	NM_014614.3	c.2614A>T	p.Ile872Leu	missense_variant	22/47	ENST00000404125.6	NP_055429.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PSME4	ENST00000404125.6	c.2614A>T	p.Ile872Leu	missense_variant	22/47	1	NM_014614.3	ENSP00000384211	P1
PSME4	ENST00000389993.7	c.*747A>T		3_prime_UTR_variant, NMD_transcript_variant	21/46	1		ENSP00000374643
PSME4	ENST00000461810.1	n.45A>T		non_coding_transcript_exon_variant	1/3	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	19
DANN	Benign	0.95
DEOGEN2	Benign	0.055	T
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.13
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.0095	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.0	N
MutationTaster	Benign	0.66	P;P
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	0.35	N
REVEL	Benign	0.048
Sift	Benign	0.50	T
Sift4G	Benign	0.47	T
Polyphen		0.0	B
Vest4		0.24
MutPred		0.32		Loss of methylation at K874 (P = 0.1124);
MVP		0.082
MPC		0.26
ClinPred		0.74	D
GERP RS		4.8
Varity_R		0.21
gMVP		0.40

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: rs2302878; hg19: chr2-54135936;