4-120694991-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BS1 BS2

The NM_018699.4(PRDM5):c.*120T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0116 in 1,207,890 control chromosomes in the GnomAD database, including 120 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.011 (18 hom., cov: 32)
  • Exomes 𝑓: 0.012 (102 hom.)
• Consequence: PRDM5 NM_018699.4 3_prime_UTR
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: 0.610

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 4-120694991-A-G is Benign according to our data. Variant chr4-120694991-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 347429.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0114 (1735/152254) while in subpopulation NFE AF= 0.0153 (1038/67994). AF 95% confidence interval is 0.0145. There are 18 homozygotes in gnomad4. There are 922 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 18 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRDM5	NM_018699.4	c.*120T>C		3_prime_UTR_variant	16/16	ENST00000264808.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRDM5	ENST00000264808.8	c.*120T>C		3_prime_UTR_variant	16/16	1	NM_018699.4	P1
PRDM5	ENST00000428209.6	c.*120T>C		3_prime_UTR_variant	15/15	1
PRDM5	ENST00000515109.5	c.*328T>C		3_prime_UTR_variant	14/14	1
PRDM5	ENST00000513741.1	n.104-9966T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0114 AC: 1735 AN: 152136 Hom.: 18 Cov.: 32

Gnomad AFR AF: 0.00227

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.0142

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00228

Gnomad FIN AF: 0.0290

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0153

Gnomad OTH AF: 0.00813

GnomAD4 exome AF: 0.0116 AC: 12286 AN: 1055636 Hom.: 102 Cov.: 14 AF XY: 0.0114 AC XY: 6207 AN XY: 542180

Gnomad4 AFR exome AF: 0.00206

Gnomad4 AMR exome AF: 0.00607

Gnomad4 ASJ exome AF: 0.00116

Gnomad4 EAS exome AF: 0.0000535

Gnomad4 SAS exome AF: 0.00229

Gnomad4 FIN exome AF: 0.0241

Gnomad4 NFE exome AF: 0.0135

Gnomad4 OTH exome AF: 0.00985

GnomAD4 genome AF: 0.0114 AC: 1735 AN: 152254 Hom.: 18 Cov.: 32 AF XY: 0.0124 AC XY: 922 AN XY: 74446

Gnomad4 AFR AF: 0.00226

Gnomad4 AMR AF: 0.0141

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00228

Gnomad4 FIN AF: 0.0290

Gnomad4 NFE AF: 0.0153

Gnomad4 OTH AF: 0.00804

Alfa AF: 0.0149 Hom.: 4

Bravo AF: 0.00914

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:1

Revision: criteria provided, conflicting classifications

Submissions by phenotype

Brittle cornea syndrome 1 Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
Cadd	Benign	8.7
Dann	Benign	0.89

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: rs77157999; hg19: chr4-121616146;