rs748520521

Variant names:

• chr20-62137380-C-G
• NM_002792.4:c.638G>C

Your query was ambiguous. Multiple possible variants found:

• chr20-62137380-C-G
• chr20-62137380-C-T

Variant summary

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

The NM_002792.4(PSMA7):​c.638G>C​(p.Arg213Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. R213Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PSMA7 NM_002792.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.83

Genes affected

PSMA7 (HGNC:9536): (proteasome 20S subunit alpha 7) The 26S proteasome is a multicatalytic proteinase complex with a highly ordered structure composed of 2 complexes, a 20S core and a 19S regulator. The 20S core 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. This gene encodes a member of the peptidase T1A family that functions as a 20S core alpha subunit. The encoded protein interacts with the hepatitis B virus X protein and plays a role in regulating hepatitis C virus internal ribosome entry site (IRES) activity, an activity essential for viral replication. The encoded protein also plays a role in the cellular stress response by regulating hypoxia-inducible factor-1alpha. A pseudogene of this gene is located on the long arm of chromosome 9. [provided by RefSeq, Jul 2012]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSMA7	NM_002792.4	c.638G>C	p.Arg213Pro	missense_variant	Exon 6 of 7	ENST00000370873.9	NP_002783.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSMA7	ENST00000370873.9	c.638G>C	p.Arg213Pro	missense_variant	Exon 6 of 7	1	NM_002792.4	ENSP00000359910.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.51
BayesDel_addAF	Uncertain	0.063	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	23
DANN	Benign	0.88
DEOGEN2	Benign	0.20	T;.
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.32
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.87	D;T
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.62	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L;.
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-1.8	N;N
REVEL	Uncertain	0.32
Sift	Benign	0.61	T;T
Sift4G	Benign	0.38	T;T
Polyphen		0.010	B;.
Vest4		0.70
MutPred		0.43		Loss of MoRF binding (P = 0.0442);.;
MVP		0.81
MPC		1.3
ClinPred		0.88	D
GERP RS		4.0
Varity_R		0.70
gMVP		0.94

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr20-60712436;