Variant 5-123090253-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.239C>T(p.Ser80Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000484 in 1,486,846 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000048 ( 1 hom. )

Consequence

PRDM6
NM_001136239.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.45

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.14868113).

BS2

High AC in GnomAd at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PRDM6	NM_001136239.4 linkuse as main transcript	c.239C>T	p.Ser80Leu	missense_variant	2/8	ENST00000407847.5
PRDM6-AS1	NR_146771.1 linkuse as main transcript	n.64G>A		non_coding_transcript_exon_variant	1/2
PRDM6	XM_047417878.1 linkuse as main transcript	c.239C>T	p.Ser80Leu	missense_variant	2/4
PRDM6	XR_001742346.2 linkuse as main transcript	n.533C>T		non_coding_transcript_exon_variant	2/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRDM6	ENST00000407847.5 linkuse as main transcript	c.239C>T	p.Ser80Leu	missense_variant	2/8	5	NM_001136239.4	P1	Q9NQX0-3
PRDM6-AS1	ENST00000458103.2 linkuse as main transcript	n.47G>A		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

AF:

0.0000529

AC:

AN:

151234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000243

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000389

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000192

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000295

Gnomad OTH

AF:

0.000484

GnomAD3 exomes

AF:

0.000120

AC:

AN:

91350

Hom.:

AF XY:

0.0000780

AC XY:

AN XY:

51260

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000177

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000162

Gnomad NFE exome

AF:

0.000198

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000479

AC:

AN:

1335506

Hom.:

Cov.:

AF XY:

0.0000395

AC XY:

AN XY:

658374

show subpopulations

Gnomad4 AFR exome

AF:

0.0000373

Gnomad4 AMR exome

AF:

0.0000688

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000587

Gnomad4 NFE exome

AF:

0.0000304

Gnomad4 OTH exome

AF:

0.0000546

GnomAD4 genome

AF:

0.0000529

AC:

AN:

151340

Hom.:

Cov.:

AF XY:

0.0000541

AC XY:

AN XY:

73984

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000390

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000192

Gnomad4 NFE

AF:

0.0000295

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.0000306

Hom.:

Bravo

AF:

0.0000491

ExAC

AF:

0.000108

AC:

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

Feb 17, 2024

The c.239C>T (p.S80L) 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 239, causing the serine (S) at amino acid position 80 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

0.15

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.51

Cadd

Uncertain

Dann

Uncertain

1.0

DEOGEN2

Benign

0.0056

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.28

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.68

M_CAP

Uncertain

0.26

MetaRNN

Benign

0.15

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.81

MutationTaster

Benign

0.56

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

-0.81

REVEL

Benign

0.082

Sift

Uncertain

0.0020

Sift4G

Benign

0.10

Polyphen

0.94

Vest4

0.18

MutPred

0.23

Loss of phosphorylation at S80 (P = 0.0013);

MVP

0.24

ClinPred

0.13

GERP RS

2.5

Varity_R

0.15

gMVP

0.37

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