Variant 5-123090172-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001136239.4(PRDM6):c.158C>T(p.Pro53Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000598 in 1,338,256 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000060 ( 0 hom. )

Consequence

PRDM6
NM_001136239.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.87

Variant links:

Genes affected

PRDM6 (HGNC:9350): (PR/SET domain 6) The protein encoded by this gene is a transcriptional repressor and a member of the PRDM family. Family members contain a PR domain and multiple zinc-finger domains. The encoded protein is involved in regulation of vascular smooth muscle cells (VSMC) contractile proteins. Mutations in this gene result in patent ductus arteriosus 3 (PDA3). [provided by RefSeq, Apr 2017]

PRDM6 links:

PRDM6-AS1 (HGNC:55869): (PRDM6 antisense RNA 1)

PRDM6-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.20054254).

BS2

High AC in GnomAdExome4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
PRDM6	NM_001136239.4 linkuse as main transcript	c.158C>T	p.Pro53Leu	missense_variant	2/8	ENST00000407847.5	NP_001129711.1
PRDM6-AS1	NR_146771.1 linkuse as main transcript	n.145G>A		non_coding_transcript_exon_variant	1/2
PRDM6	XM_047417878.1 linkuse as main transcript	c.158C>T	p.Pro53Leu	missense_variant	2/4		XP_047273834.1
PRDM6	XR_001742346.2 linkuse as main transcript	n.452C>T		non_coding_transcript_exon_variant	2/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRDM6	ENST00000407847.5 linkuse as main transcript	c.158C>T	p.Pro53Leu	missense_variant	2/8	5	NM_001136239.4	ENSP00000384725	P1	Q9NQX0-3
PRDM6-AS1	ENST00000458103.2 linkuse as main transcript	n.128G>A		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000598

AC:

AN:

1338256

Hom.:

Cov.:

AF XY:

0.00000303

AC XY:

AN XY:

659586

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000138

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000379

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 26, 2023

The c.158C>T (p.P53L) alteration is located in exon 2 (coding exon 1) of the PRDM6 gene. This alteration results from a C to T substitution at nucleotide position 158, causing the proline (P) at amino acid position 53 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.0035

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.44

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.60

M_CAP

Uncertain

0.24

MetaRNN

Benign

0.20

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.0

MutationTaster

Benign

0.99

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

0.28

REVEL

Benign

0.13

Sift

Benign

0.25

Sift4G

Uncertain

0.0030

Polyphen

0.97

Vest4

0.33

MutPred

0.22

Loss of glycosylation at P53 (P = 0.0011);

MVP

0.26

ClinPred

0.43

GERP RS

2.6

Varity_R

0.046

gMVP

0.21

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