Genetic Variant ROGDI:p.Asp69Asp (chr16-4801315-G-A) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_024589.3(ROGDI):c.207C>T(p.Asp69Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,455,828 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ROGDI
NM_024589.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.89

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant 16-4801315-G-A is Benign according to our data. Variant chr16-4801315-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 700278.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=2.89 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROGDI	NM_024589.3	MANE Select	c.207C>T	p.Asp69Asp	synonymous	Exon 4 of 11	NP_078865.1
	ROGDI	NR_046480.2		n.262+188C>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ROGDI	ENST00000322048.12	TSL:1 MANE Select	c.207C>T	p.Asp69Asp	synonymous	Exon 4 of 11	ENSP00000322832.6
ROGDI	ENST00000591392.5	TSL:3	c.135C>T	p.Asp45Asp	synonymous	Exon 3 of 9	ENSP00000467509.1
ROGDI	ENST00000585653.1	TSL:5	n.339C>T		non_coding_transcript_exon	Exon 3 of 6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000405

AC:

AN:

246786

AF XY:

0.00000749

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000293

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1455828

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

723368

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33380

American (AMR)

AF:

0.0000225

AC:

AN:

44352

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25824

East Asian (EAS)

AF:

0.00

AC:

AN:

39570

South Asian (SAS)

AF:

0.00

AC:

AN:

85764

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53256

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5734

European-Non Finnish (NFE)

AF:

9.03e-7

AC:

AN:

1107908

Other (OTH)

AF:

0.0000167

AC:

AN:

60040

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

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:

0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Amelocerebrohypohidrotic syndrome

Benign:1

Feb 09, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

9.5

(source)

DANN

Benign

0.85

PhyloP100

2.9

PromoterAI

0.068

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.17

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

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over