Variant 4-120694991-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

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

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 0.610

Variant links:

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 links:

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ACMG classification

Classification made for transcript

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: {Uncertain_significance=1, Likely_benign=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 GnomAd4 at 18 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRDM5	NM_018699.4 link	c.*120T>C		3_prime_UTR_variant	Exon 16 of 16	ENST00000264808.8	NP_061169.2	Q9NQX1-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
PRDM5	ENST00000264808 link	c.*120T>C	3_prime_UTR_variant	Exon 16 of 16	1	NM_018699.4	ENSP00000264808.3	Q9NQX1-1
PRDM5	ENST00000428209 link	c.*120T>C	3_prime_UTR_variant	Exon 15 of 15	1		ENSP00000404832.2	Q9NQX1-2
PRDM5	ENST00000515109 link	c.*328T>C	3_prime_UTR_variant	Exon 14 of 14	1		ENSP00000422309.1	Q9NQX1-4
PRDM5	ENST00000513741.1 link	n.104-9966T>C	intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes

AF:

0.0114

AC:

1735

AN:

152136

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.0114

AC XY:

6207

AN XY:

542180

show subpopulations

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.:

Cov.:

AF XY:

0.0124

AC XY:

922

AN XY:

74446

show subpopulations

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.:

Bravo

AF:

0.00914

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Brittle cornea syndrome 1

Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Jun 26, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over