chr19-1753690-G-A

Position:

• chr19-1753690-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001080488.2(ONECUT3):​c.28G>A​(p.Gly10Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000019 in 1,051,098 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000067 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000011 (0 hom.)
• Consequence: ONECUT3 NM_001080488.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.84

Genes affected

ONECUT3 (HGNC:13399): (one cut homeobox 3) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be part of chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.039605737).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ONECUT3	NM_001080488.2	c.28G>A	p.Gly10Ser	missense_variant	1/2	ENST00000382349.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ONECUT3	ENST00000382349.5	c.28G>A	p.Gly10Ser	missense_variant	1/2	5	NM_001080488.2	P1

Frequencies

GnomAD3 genomes AF: 0.00000675 AC: 1 AN: 148240 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000196

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000111 AC: 1 AN: 902858 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 422330

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000114

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 AF: 0.00000675 AC: 1 AN: 148240 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 72192

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000196

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0022	T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.071	D
MetaRNN	Benign	0.040	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.12	N
MutationTaster	Benign	0.99	N
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	0.53	N
REVEL	Benign	0.085
Sift	Benign	0.54	T
Sift4G	Benign	0.88	T
Polyphen		0.075	B
Vest4		0.060
MutPred		0.053		Gain of helix (P = 0.0325);
MVP		0.28
ClinPred		0.22	T
GERP RS		3.0
Varity_R		0.086

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: rs1487408410; hg19: chr19-1753689;