Variant 5-123090213-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001136239.4(PRDM6):c.199G>A(p.Asp67Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00105 in 1,479,642 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00073 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0011 ( 0 hom. )

Consequence

PRDM6
NM_001136239.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.50

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011134952).

BS2

High AC in GnomAd at 111 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PRDM6	NM_001136239.4 linkuse as main transcript	c.199G>A	p.Asp67Asn	missense_variant	2/8	ENST00000407847.5
PRDM6-AS1	NR_146771.1 linkuse as main transcript	n.104C>T		non_coding_transcript_exon_variant	1/2
PRDM6	XM_047417878.1 linkuse as main transcript	c.199G>A	p.Asp67Asn	missense_variant	2/4
PRDM6	XR_001742346.2 linkuse as main transcript	n.493G>A		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.199G>A	p.Asp67Asn	missense_variant	2/8	5	NM_001136239.4	P1	Q9NQX0-3
PRDM6-AS1	ENST00000458103.2 linkuse as main transcript	n.87C>T		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

AF:

0.000732

AC:

111

AN:

151696

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000218

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00190

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00103

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000612

AC:

AN:

83364

Hom.:

AF XY:

0.000527

AC XY:

AN XY:

47470

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00164

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000104

Gnomad NFE exome

AF:

0.000829

Gnomad OTH exome

AF:

0.000433

GnomAD4 exome

AF:

0.00108

AC:

1440

AN:

1327842

Hom.:

Cov.:

AF XY:

0.00106

AC XY:

697

AN XY:

654640

show subpopulations

Gnomad4 AFR exome

AF:

0.000263

Gnomad4 AMR exome

AF:

0.00166

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000475

Gnomad4 NFE exome

AF:

0.00127

Gnomad4 OTH exome

AF:

0.000897

GnomAD4 genome

AF:

0.000731

AC:

111

AN:

151800

Hom.:

Cov.:

AF XY:

0.000647

AC XY:

AN XY:

74206

show subpopulations

Gnomad4 AFR

AF:

0.000217

Gnomad4 AMR

AF:

0.00190

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00103

Gnomad4 OTH

AF:

0.00143

Alfa

AF:

0.000464

Hom.:

Bravo

AF:

0.000858

ExAC

AF:

0.000128

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

Jul 14, 2021

The c.199G>A (p.D67N) alteration is located in exon 2 (coding exon 1) of the PRDM6 gene. This alteration results from a G to A substitution at nucleotide position 199, causing the aspartic acid (D) at amino acid position 67 to be replaced by an asparagine (N). 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

0.26

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.68

Cadd

Benign

Dann

Uncertain

0.98

DEOGEN2

Benign

0.0034

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.82

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.62

M_CAP

Uncertain

0.18

MetaRNN

Benign

0.011

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.69

MutationTaster

Benign

0.74

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-0.23

REVEL

Benign

0.043

Sift

Benign

0.16

Sift4G

Benign

0.30

Polyphen

0.20

Vest4

0.17

MVP

0.18

ClinPred

0.093

GERP RS

2.4

Varity_R

0.046

gMVP

0.27

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