rs138409264

Positions:

chr16-4797823-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_024589.3(ROGDI):c.713G>A(p.Arg238His) variant causes a missense change. The variant allele was found at a frequency of 0.00558 in 1,612,036 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0052 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0056 ( 34 hom. )

Consequence

ROGDI
NM_024589.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 5.15

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 links:

ROGDI (HGNC:):

ROGDI links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009333074).

BP6

Variant 16-4797823-C-T is Benign according to our data. Variant chr16-4797823-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 319399.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-4797823-C-T is described in Lovd as [Likely_benign]. Variant chr16-4797823-C-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00517 (787/152230) while in subpopulation NFE AF= 0.00563 (383/68002). AF 95% confidence interval is 0.00517. There are 1 homozygotes in gnomad4. There are 394 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 34 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ROGDI	NM_024589.3 linkuse as main transcript	c.713G>A	p.Arg238His	missense_variant	10/11	ENST00000322048.12	NP_078865.1	Q9GZN7
ROGDI	XM_006720947.5 linkuse as main transcript	c.734G>A	p.Arg245His	missense_variant	10/11		XP_006721010.1
ROGDI	XM_047434636.1 linkuse as main transcript	c.464G>A	p.Arg155His	missense_variant	8/9		XP_047290592.1
ROGDI	NR_046480.2 linkuse as main transcript	n.720G>A		non_coding_transcript_exon_variant	9/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ROGDI	ENST00000322048.12 linkuse as main transcript	c.713G>A	p.Arg238His	missense_variant	10/11	1	NM_024589.3	ENSP00000322832.6		Q9GZN7

Frequencies

GnomAD3 genomes

AF:

0.00517

AC:

787

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00529

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00321

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0124

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00563

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00484

AC:

1207

AN:

249204

Hom.:

AF XY:

0.00472

AC XY:

637

AN XY:

134988

show subpopulations

Gnomad AFR exome

AF:

0.00495

Gnomad AMR exome

AF:

0.00255

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.0138

Gnomad NFE exome

AF:

0.00645

Gnomad OTH exome

AF:

0.00393

GnomAD4 exome

AF:

0.00562

AC:

8204

AN:

1459806

Hom.:

Cov.:

AF XY:

0.00541

AC XY:

3926

AN XY:

726338

show subpopulations

Gnomad4 AFR exome

AF:

0.00591

Gnomad4 AMR exome

AF:

0.00318

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000267

Gnomad4 FIN exome

AF:

0.0128

Gnomad4 NFE exome

AF:

0.00618

Gnomad4 OTH exome

AF:

0.00487

GnomAD4 genome

AF:

0.00517

AC:

787

AN:

152230

Hom.:

Cov.:

AF XY:

0.00529

AC XY:

394

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.00527

Gnomad4 AMR

AF:

0.00320

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0124

Gnomad4 NFE

AF:

0.00563

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00544

Hom.:

Bravo

AF:

0.00475

TwinsUK

AF:

0.00782

AC:

ALSPAC

AF:

0.00493

AC:

ESP6500AA

AF:

0.00592

AC:

ESP6500EA

AF:

0.00558

AC:

ExAC

AF:

0.00518

AC:

629

EpiCase

AF:

0.00431

EpiControl

AF:

0.00551

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Oct 12, 2016	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Oct 01, 2024	ENSG00000285952: BS2; ROGDI: BS2 -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Sep 27, 2017	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Amelocerebrohypohidrotic syndrome

Benign:4

Likely benign, 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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -
Likely benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Mendelics	May 28, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -

not specified

Benign:1

Benign, no assertion criteria provided

clinical testing

Genome Diagnostics Laboratory, University Medical Center Utrecht

- -

ROGDI-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 20, 2023

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Benign

-0.14

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.0064

Eigen

Uncertain

0.22

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.28

MetaRNN

Benign

0.0093

MVP

0.27

ClinPred

0.085

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over