rs883534

Variant names:

• chr4-120898385-T-C
• rs883534
• NM_018699.4:c.177+9089A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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]

PRDM5 Gene-Disease associations (from GenCC):

• brittle cornea syndrome 2

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, PanelApp Australia
• brittle cornea syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• aortic disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• Axenfeld-Rieger syndrome

  Inheritance: AD Classification: LIMITED Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 25 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018699.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRDM5	NM_018699.4	MANE Select	c.177+9089A>G		intron	N/A	NP_061169.2
	PRDM5	NM_001379104.1		c.177+9089A>G		intron	N/A	NP_001366033.1
	PRDM5	NM_001300823.2		c.177+9089A>G		intron	N/A	NP_001287752.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRDM5	ENST00000264808.8	TSL:1 MANE Select	c.177+9089A>G		intron	N/A	ENSP00000264808.3
	PRDM5	ENST00000428209.6	TSL:1	c.177+9089A>G		intron	N/A	ENSP00000404832.2
	PRDM5	ENST00000515109.5	TSL:1	c.177+9089A>G		intron	N/A	ENSP00000422309.1

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

African (AFR) AF: 0.00334 AC: 139 AN: 41586

American (AMR) AF: 0.0148 AC: 226 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0421 AC: 146 AN: 3470

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5188

South Asian (SAS) AF: 0.0307 AC: 148 AN: 4826

European-Finnish (FIN) AF: 0.00489 AC: 52 AN: 10624

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0164 AC: 1113 AN: 68034

Other (OTH) AF: 0.0203 AC: 43 AN: 2116

Alfa AF: 0.0165 Hom.: 34

Bravo AF: 0.0127

Asia WGS AF: 0.0120 AC: 40 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.3
DANN	Benign	0.62
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs883534; hg19: chr4-121819540;