chr2-53908799-T-C

Variant names:

• chr2-53908799-T-C
• rs2302878
• NM_014614.3:c.2614A>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_014614.3(PSME4):​c.2614A>G​(p.Ile872Val) variant causes a missense change. The variant allele was found at a frequency of 0.0325 in 1,602,856 control chromosomes in the GnomAD database, including 3,431 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

• Frequency:
  • Genomes: 𝑓 0.050 (371 hom., cov: 32)
  • Exomes 𝑓: 0.031 (3060 hom.)
• Consequence: PSME4 NM_014614.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.86
• Publications: 13 publications found

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

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014614.3. 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
	PSME4	NM_014614.3	MANE Select	c.2614A>G	p.Ile872Val	missense	Exon 22 of 47	NP_055429.2	Q14997-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSME4	ENST00000404125.6	TSL:1 MANE Select	c.2614A>G	p.Ile872Val	missense	Exon 22 of 47	ENSP00000384211.1	Q14997-1
	PSME4	ENST00000389993.7	TSL:1	n.*747A>G		non_coding_transcript_exon	Exon 21 of 46	ENSP00000374643.3	F8WBH5
	PSME4	ENST00000389993.7	TSL:1	n.*747A>G		3_prime_UTR	Exon 21 of 46	ENSP00000374643.3	F8WBH5

Frequencies

GnomAD3 genomes AF: 0.0503 AC: 7648 AN: 151952 Hom.: 369 Cov.: 32

Gnomad AFR AF: 0.0856

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0682

Gnomad ASJ AF: 0.0130

Gnomad EAS AF: 0.219

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.0498

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0106

Gnomad OTH AF: 0.0407

GnomAD2 exomes AF: 0.0615 AC: 15269 AN: 248404 AF XY: 0.0589

Gnomad AFR exome AF: 0.0849

Gnomad AMR exome AF: 0.125

Gnomad ASJ exome AF: 0.0141

Gnomad EAS exome AF: 0.201

Gnomad FIN exome AF: 0.0443

Gnomad NFE exome AF: 0.0105

Gnomad OTH exome AF: 0.0465

GnomAD4 exome AF: 0.0306 AC: 44460 AN: 1450786 Hom.: 3060 Cov.: 29 AF XY: 0.0324 AC XY: 23395 AN XY: 722372

African (AFR) AF: 0.0820 AC: 2697 AN: 32910

American (AMR) AF: 0.117 AC: 5132 AN: 43760

Ashkenazi Jewish (ASJ) AF: 0.0132 AC: 342 AN: 25876

East Asian (EAS) AF: 0.280 AC: 11039 AN: 39424

South Asian (SAS) AF: 0.113 AC: 9682 AN: 85466

European-Finnish (FIN) AF: 0.0432 AC: 2303 AN: 53322

Middle Eastern (MID) AF: 0.0375 AC: 214 AN: 5702

European-Non Finnish (NFE) AF: 0.00978 AC: 10797 AN: 1104460

Other (OTH) AF: 0.0377 AC: 2254 AN: 59866

GnomAD4 genome AF: 0.0504 AC: 7661 AN: 152070 Hom.: 371 Cov.: 32 AF XY: 0.0544 AC XY: 4041 AN XY: 74344

African (AFR) AF: 0.0855 AC: 3551 AN: 41516

American (AMR) AF: 0.0687 AC: 1049 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.0130 AC: 45 AN: 3466

East Asian (EAS) AF: 0.219 AC: 1133 AN: 5164

South Asian (SAS) AF: 0.113 AC: 543 AN: 4810

European-Finnish (FIN) AF: 0.0498 AC: 527 AN: 10592

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0106 AC: 720 AN: 67942

Other (OTH) AF: 0.0413 AC: 87 AN: 2108

Alfa AF: 0.0276 Hom.: 935

Bravo AF: 0.0530

TwinsUK AF: 0.00755 AC: 28

ALSPAC AF: 0.00960 AC: 37

ESP6500AA AF: 0.0888 AC: 391

ESP6500EA AF: 0.0101 AC: 87

ExAC AF: 0.0612 AC: 7423

Asia WGS AF: 0.139 AC: 483 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	22
DANN	Benign	0.96
DEOGEN2	Benign	0.067	T
Eigen	Benign	-0.11
Eigen_PC	Benign	0.096
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.76	T
MetaRNN	Benign	0.0014	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		3.9
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.19	N
REVEL	Benign	0.13
Sift	Benign	0.077	T
Sift4G	Benign	0.85	T
Polyphen		0.0010	B
Vest4		0.031
MPC		0.22
ClinPred		0.019	T
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.090
gMVP		0.22
Mutation Taster		=90/10	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.22		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.22		Position offset: 1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2302878; hg19: chr2-54135936; COSMIC: COSV66366125;