dbSNP rs137912684: ROGDI:p.Gln270Gln (chr16-4797726-C-T) – ACMG Classification: Benign (-15 pts)

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS1

The NM_024589.3(ROGDI):c.810G>A(p.Gln270Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000135 in 1,309,570 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000079 ( 1 hom. )

Consequence

ROGDI
NM_024589.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.827

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: Benign. The variant received -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP6

Variant 16-4797726-C-T is Benign according to our data. Variant chr16-4797726-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 530801.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.827 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00131 (78/59700) while in subpopulation AFR AF = 0.00542 (75/13850). AF 95% confidence interval is 0.00443. There are 0 homozygotes in GnomAd4. There are 40 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

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.810G>A	p.Gln270Gln	synonymous	Exon 10 of 11	NP_078865.1	Q9GZN7
	ROGDI	NR_046480.2		n.817G>A		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.810G>A	p.Gln270Gln	synonymous	Exon 10 of 11	ENSP00000322832.6	Q9GZN7
ROGDI	ENST00000586504.5	TSL:5	c.538G>A	p.Ala180Thr	missense	Exon 6 of 7	ENSP00000465076.1	K7EJ96
ROGDI	ENST00000907806.1		c.849G>A	p.Gln283Gln	synonymous	Exon 10 of 11	ENSP00000577865.1

Frequencies

GnomAD3 genomes

AF:

0.00131

AC:

AN:

59654

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00543

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000396

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:

0.0000351

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000156

AC:

AN:

244082

AF XY:

0.000106

show subpopulations

Gnomad AFR exome

AF:

0.00188

Gnomad AMR exome

AF:

0.000273

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:

0.0000792

AC:

AN:

1249870

Hom.:

Cov.:

AF XY:

0.0000681

AC XY:

AN XY:

617046

show subpopulations

African (AFR)

AF:

0.00275

AC:

AN:

26544

American (AMR)

AF:

0.000320

AC:

AN:

34394

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19200

East Asian (EAS)

AF:

0.00

AC:

AN:

28154

South Asian (SAS)

AF:

0.0000150

AC:

AN:

66886

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39822

Middle Eastern (MID)

AF:

0.000414

AC:

AN:

4836

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

982670

Other (OTH)

AF:

0.000253

AC:

AN:

47364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

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:

0.00131

AC:

AN:

59700

Hom.:

Cov.:

AF XY:

0.00136

AC XY:

AN XY:

29482

show subpopulations

African (AFR)

AF:

0.00542

AC:

AN:

13850

American (AMR)

AF:

0.000395

AC:

AN:

5064

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1396

East Asian (EAS)

AF:

0.00

AC:

AN:

2866

South Asian (SAS)

AF:

0.00

AC:

AN:

2008

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

138

European-Non Finnish (NFE)

AF:

0.0000351

AC:

AN:

28468

Other (OTH)

AF:

0.00

AC:

AN:

838

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

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:

0.000579

Hom.:

Bravo

AF:

0.000597

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Amelocerebrohypohidrotic syndrome (1)

not provided (1)

ROGDI-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

7.4

(source)

DANN

Benign

0.67

PhyloP100

0.83

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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