Genetic Variant NM_001136239.4:c.140C>G (chr5-123090154-C-G) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001136239.4(PRDM6):c.140C>G(p.Pro47Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00137 in 1,521,304 control chromosomes in the GnomAD database, including 1 homozygotes. 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 Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00095 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0014 ( 1 hom. )

Consequence

PRDM6
NM_001136239.4 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.692

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 Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.021227002).

BP6

Variant 5-123090154-C-G is Benign according to our data. Variant chr5-123090154-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 3356848.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 145 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRDM6	NM_001136239.4 link	c.140C>G	p.Pro47Arg	missense_variant	Exon 2 of 8	ENST00000407847.5	NP_001129711.1	Q9NQX0-3
PRDM6	XM_047417878.1 link	c.140C>G	p.Pro47Arg	missense_variant	Exon 2 of 4		XP_047273834.1
PRDM6-AS1	NR_146771.1 link	n.163G>C		non_coding_transcript_exon_variant	Exon 1 of 2
PRDM6	XR_001742346.2 link	n.434C>G		non_coding_transcript_exon_variant	Exon 2 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRDM6	ENST00000407847.5 link	c.140C>G	p.Pro47Arg	missense_variant	Exon 2 of 8	5	NM_001136239.4	ENSP00000384725.3		Q9NQX0-3
PRDM6-AS1	ENST00000458103.2 link	n.146G>C		non_coding_transcript_exon_variant	Exon 1 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.000954

AC:

145

AN:

151974

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000946

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00175

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000575

AC:

AN:

111250

Hom.:

AF XY:

0.000616

AC XY:

AN XY:

61676

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000566

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000351

Gnomad NFE exome

AF:

0.00120

Gnomad OTH exome

AF:

0.000625

GnomAD4 exome

AF:

0.00142

AC:

1938

AN:

1369228

Hom.:

Cov.:

AF XY:

0.00142

AC XY:

961

AN XY:

675104

show subpopulations

Gnomad4 AFR exome

AF:

0.000321

Gnomad4 AMR exome

AF:

0.000453

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000130

Gnomad4 FIN exome

AF:

0.000238

Gnomad4 NFE exome

AF:

0.00170

Gnomad4 OTH exome

AF:

0.00159

GnomAD4 genome

AF:

0.000953

AC:

145

AN:

152076

Hom.:

Cov.:

AF XY:

0.000740

AC XY:

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000946

Gnomad4 NFE

AF:

0.00175

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.00163

Hom.:

Bravo

AF:

0.00109

ExAC

AF:

0.0000544

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PRDM6-related disorder

Benign:1

May 25, 2024

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.72

CADD

Benign

DANN

Benign

0.87

DEOGEN2

Benign

0.0029

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.35

M_CAP

Uncertain

0.15

MetaRNN

Benign

0.021

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.0

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-0.81

REVEL

Benign

0.025

Sift

Benign

0.19

Sift4G

Uncertain

0.017

Polyphen

0.0

Vest4

0.21

MVP

0.085

ClinPred

0.030

GERP RS

1.0

Varity_R

0.041

gMVP

0.26

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