16-4797348-G-A

Variant names:

• chr16-4797348-G-A
• rs886052036
• NM_024589.3:c.*112C>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.*112C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000534 in 749,736 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 Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000053 (0 hom.)
• Consequence: ROGDI NM_024589.3 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.28
• 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=-0.86).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ROGDI	NM_024589.3	c.*112C>T		3_prime_UTR_variant	Exon 11 of 11	ENST00000322048.12	NP_078865.1
ROGDI	NR_046480.2	n.983C>T		non_coding_transcript_exon_variant	Exon 10 of 10
ROGDI	XM_006720947.5	c.*112C>T		3_prime_UTR_variant	Exon 11 of 11		XP_006721010.1
ROGDI	XM_047434636.1	c.*112C>T		3_prime_UTR_variant	Exon 9 of 9		XP_047290592.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ROGDI	ENST00000322048.12	c.*112C>T		3_prime_UTR_variant	Exon 11 of 11	1	NM_024589.3	ENSP00000322832.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000534 AC: 4 AN: 749736 Hom.: 0 Cov.: 10 AF XY: 0.00000518 AC XY: 2 AN XY: 386472

African (AFR) AF: 0.00 AC: 0 AN: 18724

American (AMR) AF: 0.00 AC: 0 AN: 25014

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15970

East Asian (EAS) AF: 0.00 AC: 0 AN: 34630

South Asian (SAS) AF: 0.00 AC: 0 AN: 55620

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46168

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2822

European-Non Finnish (NFE) AF: 0.00000777 AC: 4 AN: 514986

Other (OTH) AF: 0.00 AC: 0 AN: 35802

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Amelocerebrohypohidrotic syndrome Uncertain:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.26
DANN	Benign	0.39
PhyloP100		-1.3

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: rs886052036; hg19: chr16-4847349;