dbSNP rs337112: PRDM6:c.*5877G>A (chr5-123193078-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001136239.4(PRDM6):c.*5877G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0892 in 152,212 control chromosomes in the GnomAD database, including 732 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.089 ( 732 hom., cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PRDM6
NM_001136239.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.37

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

familial patent arterial duct
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
patent ductus arteriosus 3
Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P

PRDM6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.12 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRDM6	NM_001136239.4 link	c.*5877G>A		3_prime_UTR_variant	Exon 8 of 8	ENST00000407847.5	NP_001129711.1	Q9NQX0-3
PRDM6	XM_011543726.4 link	c.*5877G>A		3_prime_UTR_variant	Exon 7 of 7		XP_011542028.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRDM6	ENST00000407847.5 link	c.*5877G>A		3_prime_UTR_variant	Exon 8 of 8	5	NM_001136239.4	ENSP00000384725.3		Q9NQX0-3

Frequencies

GnomAD3 genomes

AF:

0.0892

AC:

13561

AN:

152092

Hom.:

729

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0503

Gnomad AMI

AF:

0.0186

Gnomad AMR

AF:

0.0709

Gnomad ASJ

AF:

0.0542

Gnomad EAS

AF:

0.0310

Gnomad SAS

AF:

0.0585

Gnomad FIN

AF:

0.117

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.122

Gnomad OTH

AF:

0.0860

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

GnomAD4 genome

AF:

0.0892

AC:

13572

AN:

152212

Hom.:

732

Cov.:

AF XY:

0.0873

AC XY:

6495

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.0503

AC:

2090

AN:

41542

American (AMR)

AF:

0.0707

AC:

1081

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.0542

AC:

188

AN:

3468

East Asian (EAS)

AF:

0.0308

AC:

160

AN:

5188

South Asian (SAS)

AF:

0.0588

AC:

283

AN:

4814

European-Finnish (FIN)

AF:

0.117

AC:

1243

AN:

10596

Middle Eastern (MID)

AF:

0.0646

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.122

AC:

8300

AN:

68002

Other (OTH)

AF:

0.0903

AC:

191

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

652

1303

1955

2606

3258

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

154

308

462

616

770

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.111

Hom.:

140

Bravo

AF:

0.0821

Asia WGS

AF:

0.0860

AC:

299

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.10

(source)

DANN

Benign

0.37

PhyloP100

-1.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over