chr17-67340942-T-A

Position:

• chr17-67340942-T-A

Variant summary

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

The NM_002816.5(PSMD12):​c.1272A>T​(p.Leu424Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: PSMD12 NM_002816.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.85

Genes affected

PSMD12 (HGNC:9557): (proteasome 26S subunit, non-ATPase 12) 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. The 19S regulator is composed of a base, which contains 6 ATPase subunits and 2 non-ATPase subunits, and a lid, which contains up to 10 non-ATPase 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 non-ATPase subunit of the 19S regulator. A pseudogene has been identified on chromosome 3. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2015]

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=0.21486151).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PSMD12	NM_002816.5	c.1272A>T	p.Leu424Phe	missense_variant	11/11	ENST00000356126.8
PSMD12	NM_174871.4	c.1212A>T	p.Leu404Phe	missense_variant	10/10
PSMD12	NM_001316341.2	c.1095A>T	p.Leu365Phe	missense_variant	13/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSMD12	ENST00000356126.8	c.1272A>T	p.Leu424Phe	missense_variant	11/11	1	NM_002816.5	P1
PSMD12	ENST00000584008.5	c.*1427A>T		3_prime_UTR_variant, NMD_transcript_variant	13/13	1
PSMD12	ENST00000357146.4	c.1212A>T	p.Leu404Phe	missense_variant	10/10	2
PSMD12	ENST00000577724.1			downstream_gene_variant		2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Stankiewicz-Isidor syndrome Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

New York Genome Center

Sep 23, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Benign	-0.054	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T;.
Eigen	Benign	-0.084
Eigen_PC	Benign	0.035
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.94	D;D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.21	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.9	L;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-1.9	N;N
REVEL	Benign	0.17
Sift	Uncertain	0.010	D;D
Sift4G	Uncertain	0.017	D;D
Polyphen		0.075	B;.
Vest4		0.30
MutPred		0.39		Gain of ubiquitination at K419 (P = 0.1047);.;
MVP		0.42
MPC		0.98
ClinPred		0.84	D
GERP RS		3.7
Varity_R		0.36
gMVP		0.54

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: chr17-65337058;