dbSNP rs915624211: PRDM6:p.Pro53Leu (chr5-123090172-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001136239.4(PRDM6):c.158C>T(p.Pro53Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000598 in 1,338,256 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P53T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000060 ( 0 hom. )

Consequence

PRDM6
NM_001136239.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.87

Publications

0 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 links:

PRDM6-AS1 (HGNC:55869): (PRDM6 antisense RNA 1)

PRDM6-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.20054254).

BS2

High AC in GnomAdExome4 at 8 AD gene.

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.158C>T	p.Pro53Leu	missense	Exon 2 of 8	NP_001129711.1	Q9NQX0-3
	PRDM6-AS1	NR_146771.1		n.145G>A		non_coding_transcript_exon	Exon 1 of 2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PRDM6	ENST00000407847.5	TSL:5 MANE Select	c.158C>T	p.Pro53Leu	missense	Exon 2 of 8	ENSP00000384725.3	Q9NQX0-3
PRDM6	ENST00000890813.1		c.158C>T	p.Pro53Leu	missense	Exon 1 of 7	ENSP00000560872.1
PRDM6-AS1	ENST00000458103.3	TSL:2	n.128G>A		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000598

AC:

AN:

1338256

Hom.:

Cov.:

AF XY:

0.00000303

AC XY:

AN XY:

659586

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26576

American (AMR)

AF:

0.00

AC:

AN:

27456

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22974

East Asian (EAS)

AF:

0.000138

AC:

AN:

29090

South Asian (SAS)

AF:

0.00

AC:

AN:

72708

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44582

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4482

European-Non Finnish (NFE)

AF:

0.00000379

AC:

AN:

1055130

Other (OTH)

AF:

0.00

AC:

AN:

55258

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.519

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.0035

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.44

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.60

M_CAP

Uncertain

0.24

MetaRNN

Benign

0.20

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.0

PhyloP100

1.9

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

0.28

REVEL

Benign

0.13

Sift

Benign

0.25

Sift4G

Uncertain

0.0030

Polyphen

0.97

Vest4

0.33

MutPred

0.22

Loss of glycosylation at P53 (P = 0.0011)

MVP

0.26

ClinPred

0.43

GERP RS

2.6

Varity_R

0.046

gMVP

0.21

Mutation Taster

=94/6

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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