rs1734373037

Variant names:

• chr4-120695145-TG-T
• rs1734373037
• NM_018699.4:c.1858delC

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PVS1_Moderate PM2 PP5_Moderate

The NM_018699.4(PRDM5):​c.1858delC​(p.His620ThrfsTer8) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PRDM5 NM_018699.4 frameshift
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 9.41
• 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: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Ambry Genetics, G2P
• 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: Likely_pathogenic. The variant received 6 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0185 CDS is truncated, and there are 1 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 4-120695145-TG-T is Pathogenic according to our data. Variant chr4-120695145-TG-T is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 981043.Status of the report is criteria_provided_single_submitter, 1 stars.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRDM5	NM_018699.4	MANE Select	c.1858delC	p.His620ThrfsTer8	frameshift	Exon 16 of 16	NP_061169.2
	PRDM5	NM_001379104.1		c.1891delC	p.His631ThrfsTer8	frameshift	Exon 16 of 16	NP_001366033.1
	PRDM5	NM_001300823.2		c.1765delC	p.His589ThrfsTer8	frameshift	Exon 15 of 15	NP_001287752.1	Q9NQX1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRDM5	ENST00000264808.8	TSL:1 MANE Select	c.1858delC	p.His620ThrfsTer8	frameshift	Exon 16 of 16	ENSP00000264808.3	Q9NQX1-1
	PRDM5	ENST00000428209.6	TSL:1	c.1765delC	p.His589ThrfsTer8	frameshift	Exon 15 of 15	ENSP00000404832.2	Q9NQX1-2
	PRDM5	ENST00000515109.5	TSL:1	c.*173delC		3_prime_UTR	Exon 14 of 14	ENSP00000422309.1	Q9NQX1-4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	-	Brittle cornea syndrome 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.4

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: rs1734373037; hg19: chr4-121616300;