rs771793763

Positions:

• chr16-4798161-C-G
• chr16-4798161-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6 BP7

The NM_024589.3(ROGDI):​c.555G>C​(p.Pro185=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000223 in 1,613,768 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000021 (0 hom.)
• Consequence: ROGDI NM_024589.3 synonymous
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:2
• Conservation: PhyloP100: -0.162

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 16-4798161-C-G is Benign according to our data. Variant chr16-4798161-C-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 461614.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1}.
• BP7: Synonymous conserved (PhyloP=-0.162 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ROGDI	NM_024589.3	c.555G>C	p.Pro185=	synonymous_variant	8/11	ENST00000322048.12	NP_078865.1
ROGDI	XM_006720947.5	c.555G>C	p.Pro185=	synonymous_variant	8/11		XP_006721010.1
ROGDI	XM_047434636.1	c.285G>C	p.Pro95=	synonymous_variant	6/9		XP_047290592.1
ROGDI	NR_046480.2	n.562G>C		non_coding_transcript_exon_variant	7/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ROGDI	ENST00000322048.12	c.555G>C	p.Pro185=	synonymous_variant	8/11	1	NM_024589.3	ENSP00000322832	P1

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152156 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

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: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000803 AC: 20 AN: 248918 Hom.: 0 AF XY: 0.0000815 AC XY: 11 AN XY: 135026

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000494

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000890

Gnomad OTH exome AF: 0.000329

GnomAD4 exome AF: 0.0000205 AC: 30 AN: 1461612 Hom.: 0 Cov.: 36 AF XY: 0.0000275 AC XY: 20 AN XY: 727116

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000358

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000117

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152156 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74330

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000393

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000453

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:2

Revision: criteria provided, conflicting classifications

Submissions by phenotype

Amelocerebrohypohidrotic syndrome Uncertain:1 Benign:1

Uncertain significance, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 03, 2024	- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Sep 06, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.6
DANN	Benign	0.46

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs771793763; hg19: chr16-4848162;