rs343166

Variant names:

• chr4-120897567-A-C
• rs343166
• NM_018699.4:c.177+9907T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018699.4(PRDM5):​c.177+9907T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 152,000 control chromosomes in the GnomAD database, including 5,682 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 0.25 (5682 hom., cov: 32)
• Consequence: PRDM5 NM_018699.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27
• Publications: 2 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.389 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRDM5	NM_018699.4	c.177+9907T>G		intron_variant	Intron 2 of 15	ENST00000264808.8	NP_061169.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRDM5	ENST00000264808.8	c.177+9907T>G		intron_variant	Intron 2 of 15	1	NM_018699.4	ENSP00000264808.3

Frequencies

GnomAD3 genomes AF: 0.255 AC: 38656 AN: 151882 Hom.: 5670 Cov.: 32

Gnomad AFR AF: 0.394

Gnomad AMI AF: 0.117

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.203

Gnomad EAS AF: 0.323

Gnomad SAS AF: 0.173

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.193

Gnomad OTH AF: 0.260

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

GnomAD4 genome AF: 0.255 AC: 38708 AN: 152000 Hom.: 5682 Cov.: 32 AF XY: 0.252 AC XY: 18700 AN XY: 74288

African (AFR) AF: 0.394 AC: 16323 AN: 41422

American (AMR) AF: 0.256 AC: 3904 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.203 AC: 703 AN: 3468

East Asian (EAS) AF: 0.323 AC: 1666 AN: 5150

South Asian (SAS) AF: 0.173 AC: 832 AN: 4822

European-Finnish (FIN) AF: 0.132 AC: 1401 AN: 10578

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.193 AC: 13136 AN: 67970

Other (OTH) AF: 0.258 AC: 544 AN: 2108

Alfa AF: 0.213 Hom.: 1994

Bravo AF: 0.274

Asia WGS AF: 0.266 AC: 924 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.5
DANN	Benign	0.74
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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: rs343166; hg19: chr4-121818722;