5-123090182-C-G

Variant names:

• chr5-123090182-C-G
• rs537520863
• NM_001136239.4:c.168C>G

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_001136239.4(PRDM6):​c.168C>G​(p.Pro56Pro) 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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.59
• Publications: 0 publications found

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

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 976 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.168C>G	p.Pro56Pro	synonymous	Exon 2 of 8	NP_001129711.1	Q9NQX0-3
	PRDM6-AS1	NR_146771.1		n.135G>C		non_coding_transcript_exon	Exon 1 of 2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRDM6	ENST00000407847.5	TSL:5 MANE Select	c.168C>G	p.Pro56Pro	synonymous	Exon 2 of 8	ENSP00000384725.3	Q9NQX0-3
	PRDM6	ENST00000890813.1		c.168C>G	p.Pro56Pro	synonymous	Exon 1 of 7	ENSP00000560872.1
	PRDM6-AS1	ENST00000458103.3	TSL:2	n.118G>C		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.00646 AC: 976 AN: 151194 Hom.: 10 Cov.: 33

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

GnomAD2 exomes AF: 0.000790 AC: 66 AN: 83572 AF XY: 0.000717

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 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.: 6 Cov.: 42 AF XY: 0.000484 AC XY: 316 AN XY: 653224

African (AFR) AF: 0.0204 AC: 540 AN: 26420

American (AMR) AF: 0.00153 AC: 41 AN: 26822

Ashkenazi Jewish (ASJ) AF: 0.0000883 AC: 2 AN: 22658

East Asian (EAS) AF: 0.00 AC: 0 AN: 28878

South Asian (SAS) AF: 0.0000416 AC: 3 AN: 72104

European-Finnish (FIN) AF: 0.0000228 AC: 1 AN: 43858

Middle Eastern (MID) AF: 0.000466 AC: 2 AN: 4288

European-Non Finnish (NFE) AF: 0.0000574 AC: 60 AN: 1045332

Other (OTH) AF: 0.00181 AC: 99 AN: 54760

GnomAD4 genome AF: 0.00645 AC: 976 AN: 151302 Hom.: 10 Cov.: 33 AF XY: 0.00624 AC XY: 462 AN XY: 74004

African (AFR) AF: 0.0223 AC: 922 AN: 41424

American (AMR) AF: 0.00277 AC: 42 AN: 15146

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3458

East Asian (EAS) AF: 0.00 AC: 0 AN: 5144

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10512

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 284

European-Non Finnish (NFE) AF: 0.0000741 AC: 5 AN: 67504

Other (OTH) AF: 0.00333 AC: 7 AN: 2100

Alfa AF: 0.000531 Hom.: 0

Bravo AF: 0.0197

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	1.3
DANN	Benign	0.72
PhyloP100		-2.6
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs537520863; hg19: chr5-122425877;