Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_024589.3(ROGDI):c.485C>T(p.Thr162Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000141 in 1,423,378 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T162N) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ROGDI
NM_024589.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.96

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: 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: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROGDI	NM_024589.3	MANE Select	c.485C>T	p.Thr162Ile	missense	Exon 7 of 11	NP_078865.1
	ROGDI	NR_046480.2		n.492C>T		non_coding_transcript_exon	Exon 6 of 10

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ROGDI	ENST00000322048.12	TSL:1 MANE Select	c.485C>T	p.Thr162Ile	missense	Exon 7 of 11	ENSP00000322832.6
ROGDI	ENST00000591392.5	TSL:3	c.413C>T	p.Thr138Ile	missense	Exon 6 of 9	ENSP00000467509.1
ROGDI	ENST00000586504.5	TSL:5	c.263C>T	p.Thr88Ile	missense	Exon 4 of 7	ENSP00000465076.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000104

AC:

AN:

192318

AF XY:

0.00000969

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000231

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000141

AC:

AN:

1423378

Hom.:

Cov.:

AF XY:

0.00000284

AC XY:

AN XY:

705066

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33286

American (AMR)

AF:

0.00

AC:

AN:

38264

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25376

East Asian (EAS)

AF:

0.00

AC:

AN:

38722

South Asian (SAS)

AF:

0.00

AC:

AN:

81390

European-Finnish (FIN)

AF:

0.00

AC:

AN:

43838

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5710

European-Non Finnish (NFE)

AF:

0.00000182

AC:

AN:

1097520

Other (OTH)

AF:

0.00

AC:

AN:

59272

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.00000844

AC:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Amelocerebrohypohidrotic syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.55

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.34

CADD

Uncertain

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.010

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.044

MetaRNN

Uncertain

0.54

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.1

PhyloP100

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

0.57

REVEL

Benign

0.28

Sift

Benign

0.70

Sift4G

Benign

0.41

Polyphen

1.0

Vest4

0.80

MutPred

0.57

Loss of disorder (P = 0.0395)

MVP

0.53

MPC

0.17

ClinPred

0.70

GERP RS

4.2

Varity_R

0.26

gMVP

0.52

Mutation Taster

=45/55

disease causing

(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

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

chr16-4798615-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over