16-4797705-C-A

Variant names:

• chr16-4797705-C-A
• rs765281930
• NM_024589.3:c.822+9G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_024589.3(ROGDI):​c.822+9G>T variant causes a intron 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.

• Frequency: Genomes: not found (cov: 38)
• Consequence: ROGDI NM_024589.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.674
• Publications: 0 publications found

Genes affected

ROGDI (HGNC:29478): (rogdi atypical leucine zipper) Involved in brain development; neurogenesis; and odontogenesis of dentin-containing tooth. Located in nuclear envelope. Implicated in Kohlschutter-Tonz syndrome. [provided by Alliance of Genome Resources, Apr 2022]

ROGDI Gene-Disease associations (from GenCC):

• amelocerebrohypohidrotic syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, ClinGen, Labcorp Genetics (formerly Invitae)

ENSG00000285952 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ROGDI	NM_024589.3	c.822+9G>T		intron_variant	Intron 10 of 10	ENST00000322048.12	NP_078865.1
ROGDI	NR_046480.2	n.829+9G>T		intron_variant	Intron 9 of 9
ROGDI	XM_006720947.5	c.843+9G>T		intron_variant	Intron 10 of 10		XP_006721010.1
ROGDI	XM_047434636.1	c.573+9G>T		intron_variant	Intron 8 of 8		XP_047290592.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ROGDI	ENST00000322048.12	c.822+9G>T		intron_variant	Intron 10 of 10	1	NM_024589.3	ENSP00000322832.6

Frequencies

GnomAD3 genomes Cov.: 38

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 38

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.77
DANN	Benign	0.46
PhyloP100		-0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs765281930; hg19: chr16-4847706;