chr16-4798091-G-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_024589.3(ROGDI):c.625C>G(p.Leu209Val) variant causes a missense change. The variant allele was found at a frequency of 0.000413 in 1,613,842 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. L209L) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0022 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00022 ( 4 hom. )

Consequence

ROGDI
NM_024589.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:3

Conservation

PhyloP100: 4.71

Publications

0 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: PanelApp Australia, G2P, Orphanet, 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 -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009756118).

BP6

Variant 16-4798091-G-C is Benign according to our data. Variant chr16-4798091-G-C is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 319401.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00223 (339/152320) while in subpopulation AFR AF = 0.00779 (324/41576). AF 95% confidence interval is 0.00709. There are 1 homozygotes in GnomAd4. There are 157 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

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.625C>G	p.Leu209Val	missense	Exon 8 of 11	NP_078865.1	Q9GZN7
	ROGDI	NR_046480.2		n.632C>G		non_coding_transcript_exon	Exon 7 of 10

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ROGDI	ENST00000322048.12	TSL:1 MANE Select	c.625C>G	p.Leu209Val	missense	Exon 8 of 11	ENSP00000322832.6	Q9GZN7
ROGDI	ENST00000907806.1		c.625C>G	p.Leu209Val	missense	Exon 8 of 11	ENSP00000577865.1
ROGDI	ENST00000912071.1		c.625C>G	p.Leu209Val	missense	Exon 8 of 11	ENSP00000582130.1

Frequencies

GnomAD3 genomes

AF:

0.00223

AC:

339

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00782

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000523

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:

0.0000588

Gnomad OTH

AF:

0.00144

GnomAD2 exomes

AF:

0.000512

AC:

128

AN:

250054

AF XY:

0.000317

show subpopulations

Gnomad AFR exome

AF:

0.00725

Gnomad AMR exome

AF:

0.000232

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000224

AC:

328

AN:

1461522

Hom.:

Cov.:

AF XY:

0.000202

AC XY:

147

AN XY:

727084

show subpopulations

African (AFR)

AF:

0.00795

AC:

266

AN:

33474

American (AMR)

AF:

0.000336

AC:

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26126

East Asian (EAS)

AF:

0.00

AC:

AN:

39692

South Asian (SAS)

AF:

0.0000348

AC:

AN:

86246

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53354

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.0000117

AC:

AN:

1111776

Other (OTH)

AF:

0.000497

AC:

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

107

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.00223

AC:

339

AN:

152320

Hom.:

Cov.:

AF XY:

0.00211

AC XY:

157

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.00779

AC:

324

AN:

41576

American (AMR)

AF:

0.000523

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68008

Other (OTH)

AF:

0.00142

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.0000856

Hom.:

Bravo

AF:

0.00234

ESP6500AA

AF:

0.00569

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000667

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

Amelocerebrohypohidrotic syndrome (2)

not provided (2)

ROGDI-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.30

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.025

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.028

MetaRNN

Benign

0.0098

MetaSVM

Benign

-0.96

MutationAssessor

Uncertain

2.1

PhyloP100

4.7

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-0.44

REVEL

Benign

0.16

Sift

Benign

0.079

Sift4G

Benign

0.061

Polyphen

1.0

Vest4

0.48

MVP

0.22

MPC

0.13

ClinPred

0.049

GERP RS

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.25

gMVP

0.51

Mutation Taster

=76/24

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over