16-4799704-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_024589.3(ROGDI):c.414G>A(p.Thr138Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 1,612,418 control chromosomes in the GnomAD database, including 16,523 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1153 hom., cov: 33)

Exomes 𝑓: 0.14 ( 15370 hom. )

Consequence

ROGDI
NM_024589.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -4.74

Publications

13 publications found

Variant links:

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)

ROGDI links:

ENSG00000285952 (HGNC:):

ENSG00000285952 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 16-4799704-C-T is Benign according to our data. Variant chr16-4799704-C-T is described in ClinVar as Benign. ClinVar VariationId is 130160.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-4.74 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
ROGDI	NM_024589.3 link	c.414G>A	p.Thr138Thr	synonymous_variant	Exon 6 of 11	ENST00000322048.12	NP_078865.1
ROGDI	XM_006720947.5 link	c.414G>A	p.Thr138Thr	synonymous_variant	Exon 6 of 11		XP_006721010.1
ROGDI	XM_047434636.1 link	c.144G>A	p.Thr48Thr	synonymous_variant	Exon 4 of 9		XP_047290592.1
ROGDI	NR_046480.2 link	n.421G>A		non_coding_transcript_exon_variant	Exon 5 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ROGDI	ENST00000322048.12 link	c.414G>A	p.Thr138Thr	synonymous_variant	Exon 6 of 11	1	NM_024589.3	ENSP00000322832.6

Frequencies

GnomAD3 genomes

AF:

0.110

AC:

16660

AN:

152090

Hom.:

1159

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0387

Gnomad AMI

AF:

0.128

Gnomad AMR

AF:

0.106

Gnomad ASJ

AF:

0.243

Gnomad EAS

AF:

0.0360

Gnomad SAS

AF:

0.201

Gnomad FIN

AF:

0.116

Gnomad MID

AF:

0.237

Gnomad NFE

AF:

0.143

Gnomad OTH

AF:

0.133

GnomAD2 exomes

AF:

0.130

AC:

32330

AN:

249506

AF XY:

0.137

show subpopulations

Gnomad AFR exome

AF:

0.0327

Gnomad AMR exome

AF:

0.0779

Gnomad ASJ exome

AF:

0.249

Gnomad EAS exome

AF:

0.0299

Gnomad FIN exome

AF:

0.121

Gnomad NFE exome

AF:

0.144

Gnomad OTH exome

AF:

0.144

GnomAD4 exome

AF:

0.140

AC:

204537

AN:

1460210

Hom.:

15370

Cov.:

AF XY:

0.143

AC XY:

103590

AN XY:

726400

show subpopulations

African (AFR)

AF:

0.0334

AC:

1117

AN:

33462

American (AMR)

AF:

0.0832

AC:

3712

AN:

44622

Ashkenazi Jewish (ASJ)

AF:

0.244

AC:

6364

AN:

26068

East Asian (EAS)

AF:

0.0521

AC:

2066

AN:

39674

South Asian (SAS)

AF:

0.204

AC:

17541

AN:

86086

European-Finnish (FIN)

AF:

0.125

AC:

6660

AN:

53362

Middle Eastern (MID)

AF:

0.180

AC:

1038

AN:

5760

European-Non Finnish (NFE)

AF:

0.141

AC:

157180

AN:

1110858

Other (OTH)

AF:

0.147

AC:

8859

AN:

60318

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

7864

15728

23593

31457

39321

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5608

11216

16824

22432

28040

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.109

AC:

16633

AN:

152208

Hom.:

1153

Cov.:

AF XY:

0.109

AC XY:

8093

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.0385

AC:

1599

AN:

41526

American (AMR)

AF:

0.106

AC:

1620

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.243

AC:

843

AN:

3468

East Asian (EAS)

AF:

0.0359

AC:

186

AN:

5184

South Asian (SAS)

AF:

0.200

AC:

964

AN:

4826

European-Finnish (FIN)

AF:

0.116

AC:

1225

AN:

10604

Middle Eastern (MID)

AF:

0.214

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.143

AC:

9738

AN:

67998

Other (OTH)

AF:

0.132

AC:

278

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

771

1543

2314

3086

3857

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

200

400

600

800

1000

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.134

Hom.:

1687

Bravo

AF:

0.104

Asia WGS

AF:

0.127

AC:

441

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

May 04, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 20, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:2

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Amelocerebrohypohidrotic syndrome

Benign:2

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.064

(source)

DANN

Benign

0.88

PhyloP100

-4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over