5-123090154-C-T

Variant names:

• chr5-123090154-C-T
• rs750141617
• NM_001136239.4:c.140C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001136239.4(PRDM6):​c.140C>T​(p.Pro47Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000073 in 1,369,234 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P47R) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: PRDM6 NM_001136239.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.692

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07158443).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRDM6	NM_001136239.4	c.140C>T	p.Pro47Leu	missense_variant	Exon 2 of 8	ENST00000407847.5	NP_001129711.1
PRDM6	XM_047417878.1	c.140C>T	p.Pro47Leu	missense_variant	Exon 2 of 4		XP_047273834.1
PRDM6-AS1	NR_146771.1	n.163G>A		non_coding_transcript_exon_variant	Exon 1 of 2
PRDM6	XR_001742346.2	n.434C>T		non_coding_transcript_exon_variant	Exon 2 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRDM6	ENST00000407847.5	c.140C>T	p.Pro47Leu	missense_variant	Exon 2 of 8	5	NM_001136239.4	ENSP00000384725.3
PRDM6-AS1	ENST00000458103.2	n.146G>A		non_coding_transcript_exon_variant	Exon 1 of 2	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000899 AC: 1 AN: 111250 Hom.: 0 AF XY: 0.0000162 AC XY: 1 AN XY: 61676

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000502

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.30e-7 AC: 1 AN: 1369234 Hom.: 0 Cov.: 45 AF XY: 0.00 AC XY: 0 AN XY: 675106

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000317

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ExAC AF: 0.0000544 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	14
DANN	Benign	0.91
DEOGEN2	Benign	0.0022	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.48	T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.072	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.0	N
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-0.93	N
REVEL	Benign	0.083
Sift	Benign	0.080	T
Sift4G	Uncertain	0.0020	D
Polyphen		0.076	B
Vest4		0.24
MutPred		0.095		Gain of helix (P = 0.0034);
MVP		0.13
ClinPred		0.045	T
GERP RS		1.0
Varity_R		0.040
gMVP		0.22

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: rs750141617; hg19: chr5-122425849;