Variant 5-123090182-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001136239.4(PRDM6):c.168C>G(p.Pro56=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00117 in 1,476,422 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0065 ( 10 hom., cov: 33)

Exomes 𝑓: 0.00056 ( 6 hom. )

Consequence

PRDM6
NM_001136239.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.59

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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 5-123090182-C-G is Benign according to our data. Variant chr5-123090182-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2600724.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-2.59 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00645 (976/151302) while in subpopulation AFR AF= 0.0223 (922/41424). AF 95% confidence interval is 0.0211. There are 10 homozygotes in gnomad4. There are 462 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 976 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
PRDM6	NM_001136239.4 linkuse as main transcript	c.168C>G	p.Pro56=	synonymous_variant	2/8	ENST00000407847.5	NP_001129711.1
PRDM6-AS1	NR_146771.1 linkuse as main transcript	n.135G>C		non_coding_transcript_exon_variant	1/2
PRDM6	XM_047417878.1 linkuse as main transcript	c.168C>G	p.Pro56=	synonymous_variant	2/4		XP_047273834.1
PRDM6	XR_001742346.2 linkuse as main transcript	n.462C>G		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.168C>G	p.Pro56=	synonymous_variant	2/8	5	NM_001136239.4	ENSP00000384725	P1	Q9NQX0-3
PRDM6-AS1	ENST00000458103.2 linkuse as main transcript	n.118G>C		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

AF:

0.00646

AC:

976

AN:

151194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0223

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00278

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:

0.0000741

Gnomad OTH

AF:

0.00337

GnomAD3 exomes

AF:

0.000790

AC:

AN:

83572

Hom.:

AF XY:

0.000717

AC XY:

AN XY:

47428

show subpopulations

Gnomad AFR exome

AF:

0.0198

Gnomad AMR exome

AF:

0.00141

Gnomad ASJ exome

AF:

0.000850

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000191

Gnomad FIN exome

AF:

0.0000857

Gnomad NFE exome

AF:

0.000481

Gnomad OTH exome

AF:

0.00217

GnomAD4 exome

AF:

0.000564

AC:

748

AN:

1325120

Hom.:

Cov.:

AF XY:

0.000484

AC XY:

316

AN XY:

653224

show subpopulations

Gnomad4 AFR exome

AF:

0.0204

Gnomad4 AMR exome

AF:

0.00153

Gnomad4 ASJ exome

AF:

0.0000883

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000416

Gnomad4 FIN exome

AF:

0.0000228

Gnomad4 NFE exome

AF:

0.0000574

Gnomad4 OTH exome

AF:

0.00181

GnomAD4 genome

AF:

0.00645

AC:

976

AN:

151302

Hom.:

Cov.:

AF XY:

0.00624

AC XY:

462

AN XY:

74004

show subpopulations

Gnomad4 AFR

AF:

0.0223

Gnomad4 AMR

AF:

0.00277

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000741

Gnomad4 OTH

AF:

0.00333

Alfa

AF:

0.000531

Hom.:

Bravo

AF:

0.0197

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 08, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

1.3

DANN

Benign

0.72

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