5-123161237-T-C

Position:

• chr5-123161237-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001136239.4(PRDM6):​c.1153+1599T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 152,186 control chromosomes in the GnomAD database, including 3,908 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 0.21 (3908 hom., cov: 33)
• Consequence: PRDM6 NM_001136239.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.393

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRDM6	NM_001136239.4	c.1153+1599T>C		intron_variant		ENST00000407847.5	NP_001129711.1
PRDM6	XM_011543726.4	c.553+1599T>C		intron_variant			XP_011542028.1
PRDM6	XM_047417878.1	c.901-9529T>C		intron_variant			XP_047273834.1
PRDM6	XR_001742346.2	n.1447+1599T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRDM6	ENST00000407847.5	c.1153+1599T>C		intron_variant		5	NM_001136239.4	ENSP00000384725	P1
PRDM6	ENST00000434521.1	c.218-9529T>C		intron_variant, NMD_transcript_variant		2		ENSP00000390919
PRDM6	ENST00000464424.1	n.344+5226T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31571 AN: 152068 Hom.: 3899 Cov.: 33

Gnomad AFR AF: 0.341

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.0186

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.199

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.208 AC: 31603 AN: 152186 Hom.: 3908 Cov.: 33 AF XY: 0.202 AC XY: 15058 AN XY: 74402

Gnomad4 AFR AF: 0.341

Gnomad4 AMR AF: 0.135

Gnomad4 ASJ AF: 0.156

Gnomad4 EAS AF: 0.0187

Gnomad4 SAS AF: 0.112

Gnomad4 FIN AF: 0.181

Gnomad4 NFE AF: 0.172

Gnomad4 OTH AF: 0.199

Alfa AF: 0.170 Hom.: 4861

Bravo AF: 0.208

Asia WGS AF: 0.0830 AC: 288 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.8
DANN	Benign	0.74

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

Other links and lift over

dbSNP: rs459743; hg19: chr5-122496931;