16-4797840-G-A

Variant names:

• chr16-4797840-G-A
• rs75818610
• NM_024589.3:c.696C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_024589.3(ROGDI):​c.696C>T​(p.Phe232Phe) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00122 in 1,611,022 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0064 (8 hom., cov: 33)
  • Exomes 𝑓: 0.00068 (17 hom.)
• Consequence: ROGDI NM_024589.3 splice_region, synonymous
• Scores: Splicing: ADA: 0.00009521
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.141
• Publications: 3 publications found

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)

ENSG00000285952 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 16-4797840-G-A is Benign according to our data. Variant chr16-4797840-G-A is described in ClinVar as Benign. ClinVar VariationId is 319400.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.141 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00637 (970/152234) while in subpopulation AFR AF = 0.0221 (919/41542). AF 95% confidence interval is 0.0209. There are 8 homozygotes in GnomAd4. There are 422 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 8 AR gene

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.696C>T	p.Phe232Phe	splice_region synonymous	Exon 10 of 11	NP_078865.1
	ROGDI	NR_046480.2		n.703C>T		splice_region non_coding_transcript_exon	Exon 9 of 10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROGDI	ENST00000322048.12	TSL:1 MANE Select	c.696C>T	p.Phe232Phe	splice_region synonymous	Exon 10 of 11	ENSP00000322832.6
	ROGDI	ENST00000586504.5	TSL:5	c.424C>T	p.Arg142*	stop_gained splice_region	Exon 6 of 7	ENSP00000465076.1
	ROGDI	ENST00000907806.1		c.735C>T	p.Ser245Ser	synonymous	Exon 10 of 11	ENSP00000577865.1

Frequencies

GnomAD3 genomes AF: 0.00637 AC: 969 AN: 152116 Hom.: 8 Cov.: 33

Gnomad AFR AF: 0.0222

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00242

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: 0.0000882

Gnomad OTH AF: 0.00383

GnomAD2 exomes AF: 0.00165 AC: 411 AN: 248354 AF XY: 0.00120

Gnomad AFR exome AF: 0.0222

Gnomad AMR exome AF: 0.00101

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000547

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000106

Gnomad OTH exome AF: 0.000821

GnomAD4 exome AF: 0.000682 AC: 995 AN: 1458788 Hom.: 17 Cov.: 37 AF XY: 0.000599 AC XY: 435 AN XY: 725840

African (AFR) AF: 0.0235 AC: 786 AN: 33478

American (AMR) AF: 0.00114 AC: 51 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39694

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50628

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5766

European-Non Finnish (NFE) AF: 0.0000657 AC: 73 AN: 1111774

Other (OTH) AF: 0.00131 AC: 79 AN: 60360

GnomAD4 genome AF: 0.00637 AC: 970 AN: 152234 Hom.: 8 Cov.: 33 AF XY: 0.00567 AC XY: 422 AN XY: 74442

African (AFR) AF: 0.0221 AC: 919 AN: 41542

American (AMR) AF: 0.00242 AC: 37 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 67994

Other (OTH) AF: 0.00379 AC: 8 AN: 2112

Alfa AF: 0.00157 Hom.: 1

Bravo AF: 0.00720

Asia WGS AF: 0.000577 AC: 3 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000237

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Amelocerebrohypohidrotic syndrome (2)
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	0.95
DANN	Benign	0.59
PhyloP100		-0.14
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9
Mutation Taster		=72/28	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000095
dbscSNV1_RF	Benign	0.042
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs75818610; hg19: chr16-4847841;