rs370716397

Variant names:

• chr15-78545761-C-G
• NM_002789.6:c.504C>G

Your query was ambiguous. Multiple possible variants found:

• chr15-78545761-C-G
• chr15-78545761-C-T

Variant summary

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

The NM_002789.6(PSMA4):​c.504C>G​(p.Ser168Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,238 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. S168N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PSMA4 NM_002789.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.602

Genes affected

PSMA4 (HGNC:9533): (proteasome 20S subunit alpha 4) This gene encodes a core alpha subunit of the 20S proteosome, which is a highly ordered ring-shaped structure composed of four rings of 28 non-identical subunits. Proteasomes cleave peptides in an ATP- and ubiquitin-dependent manner. [provided by RefSeq, Aug 2016]

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
PSMA4	NM_002789.6	c.504C>G	p.Ser168Arg	missense_variant	Exon 7 of 9	ENST00000044462.12	NP_002780.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSMA4	ENST00000044462.12	c.504C>G	p.Ser168Arg	missense_variant	Exon 7 of 9	1	NM_002789.6	ENSP00000044462.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461238 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726930

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: 9.00e-7

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	Pathogenic	0.99
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.030
CADD	Benign	11
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	.;T;T;.;.;.;T;T;T;.;T;T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.39	N
LIST_S2	Pathogenic	0.98	D;.;D;D;D;D;D;D;D;D;D;D
M_CAP	Benign	0.051	D
MetaRNN	Uncertain	0.69	D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	.;L;L;.;.;.;.;.;.;.;.;.
PrimateAI	Pathogenic	0.85	D
PROVEAN	Uncertain	-3.1	D;D;D;D;D;D;D;D;D;D;D;D
REVEL	Uncertain	0.34
Sift	Uncertain	0.025	D;T;T;T;D;T;T;T;T;T;T;D
Sift4G	Benign	0.099	T;T;T;T;T;T;T;T;T;T;T;D
Polyphen		1.0	.;D;D;.;.;.;.;.;.;.;.;.
Vest4		0.87
MutPred		0.53		.;Gain of methylation at S168 (P = 0.0472);Gain of methylation at S168 (P = 0.0472);.;.;.;Gain of methylation at S168 (P = 0.0472);Gain of methylation at S168 (P = 0.0472);Gain of methylation at S168 (P = 0.0472);Gain of methylation at S168 (P = 0.0472);.;.;
MVP		0.75
MPC		0.83
ClinPred		0.99	D
GERP RS		-5.3
Varity_R		0.78
gMVP		0.98

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: chr15-78838103;