15-52757684-C-G

Variant names:

• chr15-52757684-C-G
• rs749522422
• NM_004498.4:c.1269G>C

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_004498.4(ONECUT1):​c.1269G>C​(p.Gly423Gly) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. G423G) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ONECUT1 NM_004498.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.488
• Publications: 1 publications found

Genes affected

ONECUT1 (HGNC:8138): (one cut homeobox 1) This gene encodes a member of the Cut homeobox family of transcription factors. Expression of the encoded protein is enriched in the liver, where it stimulates transcription of liver-expressed genes, and antagonizes glucocorticoid-stimulated gene transcription. This gene may influence a variety of cellular processes including glucose metabolism, cell cycle regulation, and it may also be associated with cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2012]

ONECUT1 Gene-Disease associations (from GenCC):

• neonatal diabetes mellitus

  Inheritance: AR Classification: STRONG Submitted by: G2P

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25460964).
• BP7: Synonymous conserved (PhyloP=0.488 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004498.4. 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
	ONECUT1	NM_004498.4	MANE Select	c.1269G>C	p.Gly423Gly	synonymous	Exon 2 of 2	NP_004489.1	Q9UBC0
	ONECUT1	NR_073510.2		n.453G>C		non_coding_transcript_exon	Exon 2 of 2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ONECUT1	ENST00000305901.7	TSL:1 MANE Select	c.1269G>C	p.Gly423Gly	synonymous	Exon 2 of 2	ENSP00000302630.4	Q9UBC0
	ONECUT1	ENST00000560699.2	TSL:3	n.752G>C		non_coding_transcript_exon	Exon 2 of 2
	ONECUT1	ENST00000561401.3	TSL:3	n.214G>C		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	6.4
DANN	Benign	0.84
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.25	T
PhyloP100		0.49
PROVEAN	Pathogenic	-6.0	D
Vest4		0.22
MVP		0.41
GERP RS		-0.56
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs749522422; hg19: chr15-53049881;