dbSNP rs143000899: ROGDI:p.Leu189Leu (chr16-4798149-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_ModerateBP6BP7

The NM_024589.3(ROGDI):c.567G>A(p.Leu189Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000665 in 1,613,988 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00060 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00067 ( 1 hom. )

Consequence

ROGDI
NM_024589.3 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:3

Conservation

PhyloP100: 1.05

Publications

2 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: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP6

Variant 16-4798149-C-T is Benign according to our data. Variant chr16-4798149-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 319402.

BP7

Synonymous conserved (PhyloP=1.05 with no splicing effect.

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.567G>A	p.Leu189Leu	synonymous	Exon 8 of 11	NP_078865.1	Q9GZN7
	ROGDI	NR_046480.2		n.574G>A		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.567G>A	p.Leu189Leu	synonymous	Exon 8 of 11	ENSP00000322832.6	Q9GZN7
ROGDI	ENST00000907806.1		c.567G>A	p.Leu189Leu	synonymous	Exon 8 of 11	ENSP00000577865.1
ROGDI	ENST00000912071.1		c.567G>A	p.Leu189Leu	synonymous	Exon 8 of 11	ENSP00000582130.1

Frequencies

GnomAD3 genomes

AF:

0.000598

AC:

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00196

Gnomad ASJ

AF:

0.00260

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000588

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000649

AC:

162

AN:

249622

AF XY:

0.000658

show subpopulations

Gnomad AFR exome

AF:

0.000124

Gnomad AMR exome

AF:

0.00194

Gnomad ASJ exome

AF:

0.000897

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000630

Gnomad OTH exome

AF:

0.00213

GnomAD4 exome

AF:

0.000672

AC:

982

AN:

1461716

Hom.:

Cov.:

AF XY:

0.000725

AC XY:

527

AN XY:

727188

show subpopulations

African (AFR)

AF:

0.000119

AC:

AN:

33478

American (AMR)

AF:

0.00188

AC:

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.00176

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53364

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000726

AC:

807

AN:

1111938

Other (OTH)

AF:

0.000646

AC:

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

109

164

218

273

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

114

152

190

<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:

0.000598

AC:

AN:

152272

Hom.:

Cov.:

AF XY:

0.000510

AC XY:

AN XY:

74464

show subpopulations

African (AFR)

AF:

0.000289

AC:

AN:

41544

American (AMR)

AF:

0.00196

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00260

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000588

AC:

AN:

68008

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

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:

0.000621

Hom.:

Bravo

AF:

0.000752

EpiCase

AF:

0.00109

EpiControl

AF:

0.000948

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 (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_noAF

Benign

-0.43

CADD

Benign

7.8

(source)

DANN

Benign

0.63

PhyloP100

1.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=97/3

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over