Genetic Variant NM_024589.3:c.783C>T (chr16-4797753-G-A) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP4_ModerateBP6

The NM_024589.3(ROGDI):c.783C>T(p.Phe261Phe) variant causes a synonymous change. The variant allele was found at a frequency of 0.000355 in 1,548,420 control chromosomes in the GnomAD database, including 2 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 0.00072 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00033 ( 1 hom. )

Consequence

ROGDI
NM_024589.3 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:4

Conservation

PhyloP100: 6.87

Publications

1 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 -3 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.32).

BP6

Variant 16-4797753-G-A is Benign according to our data. Variant chr16-4797753-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 241507.

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.783C>T	p.Phe261Phe	synonymous	Exon 10 of 11	NP_078865.1	Q9GZN7
	ROGDI	NR_046480.2		n.790C>T		non_coding_transcript_exon	Exon 9 of 10

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ROGDI	ENST00000322048.12	TSL:1 MANE Select	c.783C>T	p.Phe261Phe	synonymous	Exon 10 of 11	ENSP00000322832.6	Q9GZN7
ROGDI	ENST00000586504.5	TSL:5	c.511C>T	p.His171Tyr	missense	Exon 6 of 7	ENSP00000465076.1	K7EJ96
ROGDI	ENST00000907806.1		c.822C>T	p.Phe274Phe	synonymous	Exon 10 of 11	ENSP00000577865.1

Frequencies

GnomAD3 genomes

AF:

0.000717

AC:

AN:

115782

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00120

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000561

Gnomad ASJ

AF:

0.0109

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00407

Gnomad NFE

AF:

0.000149

Gnomad OTH

AF:

0.00129

GnomAD2 exomes

AF:

0.000446

AC:

112

AN:

251260

AF XY:

0.000390

show subpopulations

Gnomad AFR exome

AF:

0.000678

Gnomad AMR exome

AF:

0.000318

Gnomad ASJ exome

AF:

0.00596

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000220

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000325

AC:

466

AN:

1432544

Hom.:

Cov.:

AF XY:

0.000324

AC XY:

231

AN XY:

712332

show subpopulations

African (AFR)

AF:

0.00219

AC:

AN:

32418

American (AMR)

AF:

0.000487

AC:

AN:

43120

Ashkenazi Jewish (ASJ)

AF:

0.00554

AC:

139

AN:

25112

East Asian (EAS)

AF:

0.00

AC:

AN:

38272

South Asian (SAS)

AF:

0.0000704

AC:

AN:

85260

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51320

Middle Eastern (MID)

AF:

0.00107

AC:

AN:

5626

European-Non Finnish (NFE)

AF:

0.000158

AC:

173

AN:

1093004

Other (OTH)

AF:

0.000856

AC:

AN:

58412

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

118

148

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:

0.000716

AC:

AN:

115876

Hom.:

Cov.:

AF XY:

0.000761

AC XY:

AN XY:

56500

show subpopulations

African (AFR)

AF:

0.00120

AC:

AN:

29966

American (AMR)

AF:

0.000560

AC:

AN:

10708

Ashkenazi Jewish (ASJ)

AF:

0.0109

AC:

AN:

2752

East Asian (EAS)

AF:

0.00

AC:

AN:

4412

South Asian (SAS)

AF:

0.00

AC:

AN:

3582

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8050

Middle Eastern (MID)

AF:

0.00435

AC:

AN:

230

European-Non Finnish (NFE)

AF:

0.000149

AC:

AN:

53844

Other (OTH)

AF:

0.00127

AC:

AN:

1570

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

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:

0.000827

Hom.:

Bravo

AF:

0.000672

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.000545

EpiControl

AF:

0.000356

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

BayesDel_noAF

Benign

-0.32

CADD

Benign

(source)

DANN

Benign

0.72

PhyloP100

6.9

Mutation Taster

=95/5

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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