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: G2P, Labcorp Genetics (formerly Invitae)

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001136239.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRDM6	NM_001136239.4	MANE Select	c.*5877G>A		3_prime_UTR	Exon 8 of 8	NP_001129711.1	Q9NQX0-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRDM6	ENST00000407847.5	TSL:5 MANE Select	c.*5877G>A		3_prime_UTR	Exon 8 of 8	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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over