15-78548878-T-C

Position:

• chr15-78548878-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_002789.6(PSMA4):​c.720T>C​(p.His240=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.608 in 1,611,738 control chromosomes in the GnomAD database, including 303,716 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.67 (34480 hom., cov: 32)
  • Exomes 𝑓: 0.60 (269236 hom.)
• Consequence: PSMA4 NM_002789.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.576

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 Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_addAF=-0.769222).
• BP7: Synonymous conserved (PhyloP=-0.576 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.817 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PSMA4	NM_002789.6	c.720T>C	p.His240=	synonymous_variant	9/9	ENST00000044462.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSMA4	ENST00000044462.12	c.720T>C	p.His240=	synonymous_variant	9/9	1	NM_002789.6	P1

Frequencies

GnomAD3 genomes AF: 0.666 AC: 101248 AN: 151946 Hom.: 34436 Cov.: 32

Gnomad AFR AF: 0.772

Gnomad AMI AF: 0.569

Gnomad AMR AF: 0.745

Gnomad ASJ AF: 0.649

Gnomad EAS AF: 0.838

Gnomad SAS AF: 0.672

Gnomad FIN AF: 0.625

Gnomad MID AF: 0.799

Gnomad NFE AF: 0.578

Gnomad OTH AF: 0.676

GnomAD3 exomes AF: 0.666 AC: 166415 AN: 250058 Hom.: 56774 AF XY: 0.660 AC XY: 89131 AN XY: 135136

Gnomad AFR exome AF: 0.780

Gnomad AMR exome AF: 0.802

Gnomad ASJ exome AF: 0.668

Gnomad EAS exome AF: 0.836

Gnomad SAS exome AF: 0.684

Gnomad FIN exome AF: 0.631

Gnomad NFE exome AF: 0.583

Gnomad OTH exome AF: 0.645

GnomAD4 exome AF: 0.602 AC: 878117 AN: 1459670 Hom.: 269236 Cov.: 49 AF XY: 0.603 AC XY: 437714 AN XY: 726040

Gnomad4 AFR exome AF: 0.781

Gnomad4 AMR exome AF: 0.796

Gnomad4 ASJ exome AF: 0.656

Gnomad4 EAS exome AF: 0.876

Gnomad4 SAS exome AF: 0.678

Gnomad4 FIN exome AF: 0.629

Gnomad4 NFE exome AF: 0.568

Gnomad4 OTH exome AF: 0.626

GnomAD4 genome AF: 0.666 AC: 101352 AN: 152068 Hom.: 34480 Cov.: 32 AF XY: 0.671 AC XY: 49884 AN XY: 74326

Gnomad4 AFR AF: 0.772

Gnomad4 AMR AF: 0.746

Gnomad4 ASJ AF: 0.649

Gnomad4 EAS AF: 0.838

Gnomad4 SAS AF: 0.673

Gnomad4 FIN AF: 0.625

Gnomad4 NFE AF: 0.578

Gnomad4 OTH AF: 0.674

Alfa AF: 0.605 Hom.: 55802

Bravo AF: 0.679

TwinsUK AF: 0.554 AC: 2054

ALSPAC AF: 0.561 AC: 2162

ESP6500AA AF: 0.759 AC: 3333

ESP6500EA AF: 0.582 AC: 5001

ExAC AF: 0.661 AC: 80236

Asia WGS AF: 0.734 AC: 2554 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.77	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.25
DANN	Benign	0.39
FATHMM_MKL	Benign	0.18	N
MutationTaster	Benign	1.0	P;P;P;P;P;P;P
Vest4		0.058
GERP RS		-7.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.8

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

LitVar

Other links and lift over

dbSNP: rs8053; hg19: chr15-78841220;