rs147894983

Variant names:

• chr2-53874403-T-C
• rs147894983
• NM_014614.3:c.5036A>G

Your query was ambiguous. Multiple possible variants found:

• chr2-53874403-T-C
• chr2-53874403-T-A
• chr2-53874403-T-G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_014614.3(PSME4):​c.5036A>G​(p.Asn1679Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000278 in 1,614,066 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/24 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00029 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00028 (0 hom.)
• Consequence: PSME4 NM_014614.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.72
• Publications: 1 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAd4 at 44 AD gene.

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.5036A>G	p.Asn1679Ser	missense	Exon 43 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.5036A>G	p.Asn1679Ser	missense	Exon 43 of 47	ENSP00000384211.1	Q14997-1
	PSME4	ENST00000389993.7	TSL:1	n.*3169A>G		non_coding_transcript_exon	Exon 42 of 46	ENSP00000374643.3	F8WBH5
	PSME4	ENST00000389993.7	TSL:1	n.*3169A>G		3_prime_UTR	Exon 42 of 46	ENSP00000374643.3	F8WBH5

Frequencies

GnomAD3 genomes AF: 0.000289 AC: 44 AN: 152176 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000573

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000259 AC: 65 AN: 251418 AF XY: 0.000213

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000185

Gnomad NFE exome AF: 0.000492

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000277 AC: 405 AN: 1461772 Hom.: 0 Cov.: 31 AF XY: 0.000278 AC XY: 202 AN XY: 727196

African (AFR) AF: 0.0000597 AC: 2 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86256

European-Finnish (FIN) AF: 0.0000936 AC: 5 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000351 AC: 390 AN: 1111922

Other (OTH) AF: 0.000116 AC: 7 AN: 60390

GnomAD4 genome AF: 0.000289 AC: 44 AN: 152294 Hom.: 0 Cov.: 32 AF XY: 0.000242 AC XY: 18 AN XY: 74468

African (AFR) AF: 0.000120 AC: 5 AN: 41550

American (AMR) AF: 0.00 AC: 0 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000573 AC: 39 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000432 Hom.: 0

Bravo AF: 0.000181

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.000371 AC: 45

EpiCase AF: 0.000218

EpiControl AF: 0.000356

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	Benign	0.068
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	22
DANN	Benign	0.94
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.32
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.0068	T
MetaRNN	Benign	0.029	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.28	N
PhyloP100		4.7
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.12
Sift	Benign	0.78	T
Sift4G	Benign	0.87	T
Polyphen		0.067	B
Vest4		0.25
MVP		0.068
MPC		0.23
ClinPred		0.037	T
GERP RS		3.4
Varity_R		0.10
gMVP		0.15
Mutation Taster		=81/19	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.32		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.32		Position offset: -1

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

Other links and lift over

dbSNP: rs147894983; hg19: chr2-54101540;