rs883534

Positions:

• chr4-120898385-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_018699.4(PRDM5):​c.177+9089A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0124 in 152,356 control chromosomes in the GnomAD database, including 25 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 0.012 (25 hom., cov: 32)
• Consequence: PRDM5 NM_018699.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.23

Genes affected

PRDM5 (HGNC:9349): (PR/SET domain 5) The protein encoded by this gene is a transcription factor of the PR-domain protein family. It contains a PR-domain and multiple zinc finger motifs. Transcription factors of the PR-domain family are known to be involved in cell differentiation and tumorigenesis. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0124 (1887/152356) while in subpopulation SAS AF= 0.0307 (148/4826). AF 95% confidence interval is 0.0266. There are 25 homozygotes in gnomad4. There are 916 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 25 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRDM5	NM_018699.4	c.177+9089A>G		intron_variant		ENST00000264808.8	NP_061169.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRDM5	ENST00000264808.8	c.177+9089A>G		intron_variant		1	NM_018699.4	ENSP00000264808	P1

Frequencies

GnomAD3 genomes AF: 0.0124 AC: 1887 AN: 152238 Hom.: 25 Cov.: 32

Gnomad AFR AF: 0.00335

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0149

Gnomad ASJ AF: 0.0421

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0306

Gnomad FIN AF: 0.00489

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0164

Gnomad OTH AF: 0.0205

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0124 AC: 1887 AN: 152356 Hom.: 25 Cov.: 32 AF XY: 0.0123 AC XY: 916 AN XY: 74504

Gnomad4 AFR AF: 0.00334

Gnomad4 AMR AF: 0.0148

Gnomad4 ASJ AF: 0.0421

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.0307

Gnomad4 FIN AF: 0.00489

Gnomad4 NFE AF: 0.0164

Gnomad4 OTH AF: 0.0203

Alfa AF: 0.0150 Hom.: 4

Bravo AF: 0.0127

Asia WGS AF: 0.0120 AC: 40 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.3
DANN	Benign	0.62

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: rs883534; hg19: chr4-121819540;