NM_014614.3:c.4188A>G

Variant names:

• chr2-53892811-T-C
• rs747915522
• NM_014614.3:c.4188A>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_014614.3(PSME4):​c.4188A>G​(p.Glu1396Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,580 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 6.9e-7 (0 hom.)
• Consequence: PSME4 NM_014614.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0360
• Publications: 0 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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP7: Synonymous conserved (PhyloP=-0.036 with no splicing effect.

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.4188A>G	p.Glu1396Glu	synonymous	Exon 36 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.4188A>G	p.Glu1396Glu	synonymous	Exon 36 of 47	ENSP00000384211.1	Q14997-1
	PSME4	ENST00000389993.7	TSL:1	n.*2321A>G		non_coding_transcript_exon	Exon 35 of 46	ENSP00000374643.3	F8WBH5
	PSME4	ENST00000389993.7	TSL:1	n.*2321A>G		3_prime_UTR	Exon 35 of 46	ENSP00000374643.3	F8WBH5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457580 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 724930

African (AFR) AF: 0.00 AC: 0 AN: 33316

American (AMR) AF: 0.00 AC: 0 AN: 43760

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25896

East Asian (EAS) AF: 0.00 AC: 0 AN: 39646

South Asian (SAS) AF: 0.00 AC: 0 AN: 85150

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53318

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5736

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1110554

Other (OTH) AF: 0.00 AC: 0 AN: 60204

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	7.5
DANN	Benign	0.61
PhyloP100		-0.036
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs747915522; hg19: chr2-54119948;