NM_024589.3:c.117+9C>G

Variant names:

• chr16-4802373-G-C
• rs374732191
• NM_024589.3:c.117+9C>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_024589.3(ROGDI):​c.117+9C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000154 in 1,567,536 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00086 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000078 (1 hom.)
• Consequence: ROGDI NM_024589.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -0.186
• 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: PanelApp Australia, G2P, Orphanet, ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 16-4802373-G-C is Benign according to our data. Variant chr16-4802373-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 461606.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024589.3. 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
	ROGDI	NM_024589.3	MANE Select	c.117+9C>G		intron	N/A	NP_078865.1	Q9GZN7
	ROGDI	NR_046480.2		n.179+9C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROGDI	ENST00000322048.12	TSL:1 MANE Select	c.117+9C>G		intron	N/A	ENSP00000322832.6	Q9GZN7
	ROGDI	ENST00000907806.1		c.117+9C>G		intron	N/A	ENSP00000577865.1
	ROGDI	ENST00000912071.1		c.117+9C>G		intron	N/A	ENSP00000582130.1

Frequencies

GnomAD3 genomes AF: 0.000861 AC: 131 AN: 152146 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00306

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000111 AC: 20 AN: 179404 AF XY: 0.0000912

Gnomad AFR exome AF: 0.00144

Gnomad AMR exome AF: 0.000148

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000777 AC: 110 AN: 1415272 Hom.: 1 Cov.: 31 AF XY: 0.0000726 AC XY: 51 AN XY: 702098

African (AFR) AF: 0.00233 AC: 74 AN: 31730

American (AMR) AF: 0.000398 AC: 15 AN: 37712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24546

East Asian (EAS) AF: 0.00 AC: 0 AN: 37544

South Asian (SAS) AF: 0.00 AC: 0 AN: 80368

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46538

Middle Eastern (MID) AF: 0.000179 AC: 1 AN: 5600

European-Non Finnish (NFE) AF: 0.00000275 AC: 3 AN: 1092818

Other (OTH) AF: 0.000291 AC: 17 AN: 58416

GnomAD4 genome AF: 0.000860 AC: 131 AN: 152264 Hom.: 0 Cov.: 33 AF XY: 0.000752 AC XY: 56 AN XY: 74452

African (AFR) AF: 0.00305 AC: 127 AN: 41582

American (AMR) AF: 0.000131 AC: 2 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67984

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000979

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Amelocerebrohypohidrotic syndrome (1)
-	-	1	ROGDI-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.3
DANN	Benign	0.51
PhyloP100		-0.19
PromoterAI		-0.0064	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism

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: rs374732191; hg19: chr16-4852374;