Variant 5-123090137-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_001136239.4(PRDM6):c.123G>T(p.Ala41=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 1,534,948 control chromosomes in the GnomAD database, including 94,767 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.32 ( 8101 hom., cov: 32)

Exomes 𝑓: 0.35 ( 86666 hom. )

Consequence

PRDM6
NM_001136239.4 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.260

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 5-123090137-G-T is Benign according to our data. Variant chr5-123090137-G-T is described in ClinVar as [Benign]. Clinvar id is 3060736.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.26 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.368 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
PRDM6	NM_001136239.4 linkuse as main transcript	c.123G>T	p.Ala41=	synonymous_variant	2/8	ENST00000407847.5	NP_001129711.1
PRDM6-AS1	NR_146771.1 linkuse as main transcript	n.180C>A		non_coding_transcript_exon_variant	1/2
PRDM6	XM_047417878.1 linkuse as main transcript	c.123G>T	p.Ala41=	synonymous_variant	2/4		XP_047273834.1
PRDM6	XR_001742346.2 linkuse as main transcript	n.417G>T		non_coding_transcript_exon_variant	2/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRDM6	ENST00000407847.5 linkuse as main transcript	c.123G>T	p.Ala41=	synonymous_variant	2/8	5	NM_001136239.4	ENSP00000384725	P1	Q9NQX0-3
PRDM6-AS1	ENST00000458103.2 linkuse as main transcript	n.163C>A		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

AF:

0.319

AC:

48364

AN:

151674

Hom.:

8092

Cov.:

show subpopulations

Gnomad AFR

AF:

0.285

Gnomad AMI

AF:

0.397

Gnomad AMR

AF:

0.322

Gnomad ASJ

AF:

0.350

Gnomad EAS

AF:

0.0334

Gnomad SAS

AF:

0.155

Gnomad FIN

AF:

0.293

Gnomad MID

AF:

0.398

Gnomad NFE

AF:

0.372

Gnomad OTH

AF:

0.358

GnomAD3 exomes

AF:

0.287

AC:

35898

AN:

125114

Hom.:

5926

AF XY:

0.282

AC XY:

19368

AN XY:

68722

show subpopulations

Gnomad AFR exome

AF:

0.305

Gnomad AMR exome

AF:

0.274

Gnomad ASJ exome

AF:

0.345

Gnomad EAS exome

AF:

0.0310

Gnomad SAS exome

AF:

0.173

Gnomad FIN exome

AF:

0.290

Gnomad NFE exome

AF:

0.382

Gnomad OTH exome

AF:

0.342

GnomAD4 exome

AF:

0.346

AC:

478104

AN:

1383166

Hom.:

86666

Cov.:

AF XY:

0.340

AC XY:

232127

AN XY:

682320

show subpopulations

Gnomad4 AFR exome

AF:

0.290

Gnomad4 AMR exome

AF:

0.281

Gnomad4 ASJ exome

AF:

0.346

Gnomad4 EAS exome

AF:

0.0332

Gnomad4 SAS exome

AF:

0.170

Gnomad4 FIN exome

AF:

0.299

Gnomad4 NFE exome

AF:

0.375

Gnomad4 OTH exome

AF:

0.329

GnomAD4 genome

AF:

0.319

AC:

48410

AN:

151782

Hom.:

8101

Cov.:

AF XY:

0.309

AC XY:

22921

AN XY:

74192

show subpopulations

Gnomad4 AFR

AF:

0.285

Gnomad4 AMR

AF:

0.322

Gnomad4 ASJ

AF:

0.350

Gnomad4 EAS

AF:

0.0333

Gnomad4 SAS

AF:

0.155

Gnomad4 FIN

AF:

0.293

Gnomad4 NFE

AF:

0.372

Gnomad4 OTH

AF:

0.361

Alfa

AF:

0.253

Hom.:

1001

Bravo

AF:

0.322

Asia WGS

AF:

0.142

AC:

495

AN:

3470

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PRDM6-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 24, 2020

This variant is classified as 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

BayesDel_noAF

Benign

-0.77

CADD

Benign

6.0

DANN

Benign

0.68

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