16-4797162-C-G

Variant names:

• chr16-4797162-C-G
• rs545854112
• NM_024589.3:c.*298G>C

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.*298G>C variant causes a 3 prime UTR 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: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ROGDI NM_024589.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.241
• 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)

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=-0.84).

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.*298G>C		3_prime_UTR	Exon 11 of 11	NP_078865.1	Q9GZN7
	ROGDI	NR_046480.2		n.1169G>C		non_coding_transcript_exon	Exon 10 of 10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROGDI	ENST00000322048.12	TSL:1 MANE Select	c.*298G>C		3_prime_UTR	Exon 11 of 11	ENSP00000322832.6	Q9GZN7
	ROGDI	ENST00000907806.1		c.*298G>C		3_prime_UTR	Exon 11 of 11	ENSP00000577865.1
	ROGDI	ENST00000912071.1		c.*298G>C		3_prime_UTR	Exon 11 of 11	ENSP00000582130.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 207962 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 109210

African (AFR) AF: 0.00 AC: 0 AN: 6524

American (AMR) AF: 0.00 AC: 0 AN: 7282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6520

East Asian (EAS) AF: 0.00 AC: 0 AN: 13608

South Asian (SAS) AF: 0.00 AC: 0 AN: 23070

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 11680

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 950

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 126174

Other (OTH) AF: 0.00 AC: 0 AN: 12154

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.1
DANN	Benign	0.75
PhyloP100		-0.24
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: rs545854112; hg19: chr16-4847163;