4-120880635-G-C

Variant names:

• chr4-120880635-G-C
• rs180730
• NM_018699.4:c.177+26839C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018699.4(PRDM5):​c.177+26839C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: PRDM5 NM_018699.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.921
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).

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+26839C>G		intron	N/A	NP_061169.2
	PRDM5	NM_001379104.1		c.177+26839C>G		intron	N/A	NP_001366033.1
	PRDM5	NM_001300823.2		c.177+26839C>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+26839C>G		intron	N/A	ENSP00000264808.3
	PRDM5	ENST00000428209.6	TSL:1	c.177+26839C>G		intron	N/A	ENSP00000404832.2
	PRDM5	ENST00000515109.5	TSL:1	c.177+26839C>G		intron	N/A	ENSP00000422309.1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.29
DANN	Benign	0.25
PhyloP100		-0.92

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: rs180730; hg19: chr4-121801790;