18-26134055-A-C

Position:

• chr18-26134055-A-C

Variant summary

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

The NM_001025096.2(PSMA8):​c.90A>C​(p.Lys30Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PSMA8 NM_001025096.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.934

Genes affected

PSMA8 (HGNC:22985): (proteasome 20S subunit alpha 8) Predicted to be involved in meiotic cell cycle and proteasomal protein catabolic process. Located in extracellular exosome and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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/exons	MANE	Protein	UniProt
PSMA8	NM_001025096.2	c.90A>C	p.Lys30Asn	missense_variant	1/7	ENST00000415576.7	NP_001020267.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PSMA8	ENST00000415576.7	c.90A>C	p.Lys30Asn	missense_variant	1/7	1	NM_001025096.2	ENSP00000409284	P3
PSMA8	ENST00000308268.10	c.90A>C	p.Lys30Asn	missense_variant	1/7	1		ENSP00000311121	A1
PSMA8	ENST00000343848.10	c.90A>C	p.Lys30Asn	missense_variant	1/7	1		ENSP00000345584
PSMA8	ENST00000538664.2	c.90A>C	p.Lys30Asn	missense_variant, NMD_transcript_variant	1/8	1		ENSP00000440327

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 10, 2023

The c.90A>C (p.K30N) alteration is located in exon 1 (coding exon 1) of the PSMA8 gene. This alteration results from a A to C substitution at nucleotide position 90, causing the lysine (K) at amino acid position 30 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Uncertain	23
DANN	Benign	0.96
DEOGEN2	Benign	0.17	.;.;T
Eigen	Benign	0.072
Eigen_PC	Benign	0.046
FATHMM_MKL	Benign	0.71	D
LIST_S2	Pathogenic	0.98	D;D;D
M_CAP	Benign	0.032	D
MetaRNN	Uncertain	0.48	T;T;T
MetaSVM	Benign	-0.97	T
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Pathogenic	0.87	D
PROVEAN	Uncertain	-3.9	D;D;D
REVEL	Benign	0.096
Sift	Uncertain	0.0010	D;D;D
Sift4G	Uncertain	0.0030	D;D;D
Polyphen		0.97	D;P;D
Vest4		0.67
MutPred		0.45		Loss of ubiquitination at K30 (P = 0.021);Loss of ubiquitination at K30 (P = 0.021);Loss of ubiquitination at K30 (P = 0.021);
MVP		0.40
MPC		0.62
ClinPred		0.99	D
GERP RS		0.26
Varity_R		0.72
gMVP		0.50

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: chr18-23714019;