rs765186274

Variant names:

• chr5-123090142-T-A
• rs765186274
• NM_001136239.4:c.128T>A

Your query was ambiguous. Multiple possible variants found:

• chr5-123090142-T-A
• chr5-123090142-T-C
• chr5-123090142-T-G

Variant summary

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

The NM_001136239.4(PRDM6):​c.128T>A​(p.Leu43His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. L43P) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PRDM6 NM_001136239.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00600

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=0.07163334).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRDM6	NM_001136239.4	c.128T>A	p.Leu43His	missense_variant	Exon 2 of 8	ENST00000407847.5	NP_001129711.1
PRDM6	XM_047417878.1	c.128T>A	p.Leu43His	missense_variant	Exon 2 of 4		XP_047273834.1
PRDM6-AS1	NR_146771.1	n.175A>T		non_coding_transcript_exon_variant	Exon 1 of 2
PRDM6	XR_001742346.2	n.422T>A		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.128T>A	p.Leu43His	missense_variant	Exon 2 of 8	5	NM_001136239.4	ENSP00000384725.3
PRDM6-AS1	ENST00000458103.2	n.158A>T		non_coding_transcript_exon_variant	Exon 1 of 2	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 46

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	11
DANN	Benign	0.85
DEOGEN2	Benign	0.0011	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.042	N
LIST_S2	Benign	0.13	T
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.072	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.0	N
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-0.45	N
REVEL	Benign	0.080
Sift	Uncertain	0.020	D
Sift4G	Benign	0.46	T
Polyphen		0.022	B
Vest4		0.21
MutPred		0.15		Loss of helix (P = 0.079);
MVP		0.067
ClinPred		0.065	T
GERP RS		-0.66
Varity_R		0.064
gMVP		0.26

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: rs765186274; hg19: chr5-122425837;