14-35313018-G-C

Variant names:

• chr14-35313018-G-C
• NM_002791.3:c.547G>C

Variant summary

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

The NM_002791.3(PSMA6):​c.547G>C​(p.Val183Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000021 in 1,427,322 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: PSMA6 NM_002791.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.80

Genes affected

PSMA6 (HGNC:9535): (proteasome 20S subunit alpha 6) The proteasome is a multicatalytic proteinase complex with a highly ordered ring-shaped 20S core structure. The core structure is composed of 4 rings of 28 non-identical subunits; 2 rings are composed of 7 alpha subunits and 2 rings are composed of 7 beta subunits. Proteasomes are distributed throughout eukaryotic cells at a high concentration and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway. An essential function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides. This gene encodes a member of the peptidase T1A family, that is a 20S core alpha subunit. Multiple transcript variants encoding several different isoforms have been found for this gene. A pseudogene has been identified on the Y chromosome. [provided by RefSeq, Aug 2013]

ENSG00000258790 (HGNC:):

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=0.10252619).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSMA6	NM_002791.3	c.547G>C	p.Val183Leu	missense_variant	Exon 5 of 7	ENST00000261479.9	NP_002782.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSMA6	ENST00000261479.9	c.547G>C	p.Val183Leu	missense_variant	Exon 5 of 7	1	NM_002791.3	ENSP00000261479.4
ENSG00000258790	ENST00000557565.1	n.*1362G>C		non_coding_transcript_exon_variant	Exon 13 of 15	2		ENSP00000454657.1
ENSG00000258790	ENST00000557565.1	n.*1362G>C		3_prime_UTR_variant	Exon 13 of 15	2		ENSP00000454657.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000210 AC: 3 AN: 1427322 Hom.: 0 Cov.: 31 AF XY: 0.00000141 AC XY: 1 AN XY: 710202

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: 0.00000272

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	0.27
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	21
DANN	Benign	0.90
DEOGEN2	Benign	0.071	.;.;T;T;.;T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.0093
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.97	D;D;D;D;.;D
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.10	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.2	.;.;N;.;.;.
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	1.2	N;.;N;N;N;N
REVEL	Benign	0.16
Sift	Benign	1.0	T;.;T;T;T;T
Sift4G	Benign	1.0	T;T;T;T;T;T
Polyphen		0.0	.;.;B;.;.;.
Vest4		0.28
MutPred		0.58		.;.;Loss of methylation at K182 (P = 0.038);.;.;Loss of methylation at K182 (P = 0.038);
MVP		0.23
MPC		0.64
ClinPred		0.74	D
GERP RS		5.6
Varity_R		0.23
gMVP		0.79

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-35782224;