rs11553876

Variant names:

• chr16-4799704-C-T
• rs11553876
• NM_024589.3:c.414G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-4799704-C-T
• chr16-4799704-C-G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_024589.3(ROGDI):​c.414G>A​(p.Thr138Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 1,612,418 control chromosomes in the GnomAD database, including 16,523 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1153 hom., cov: 33)
  • Exomes 𝑓: 0.14 (15370 hom.)
• Consequence: ROGDI NM_024589.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -4.74
• Publications: 13 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: PanelApp Australia, G2P, Orphanet, 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=-0.72).
• BP6: Variant 16-4799704-C-T is Benign according to our data. Variant chr16-4799704-C-T is described in ClinVar as Benign. ClinVar VariationId is 130160.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-4.74 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

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.414G>A	p.Thr138Thr	synonymous	Exon 6 of 11	NP_078865.1	Q9GZN7
	ROGDI	NR_046480.2		n.421G>A		non_coding_transcript_exon	Exon 5 of 10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROGDI	ENST00000322048.12	TSL:1 MANE Select	c.414G>A	p.Thr138Thr	synonymous	Exon 6 of 11	ENSP00000322832.6	Q9GZN7
	ROGDI	ENST00000907806.1		c.414G>A	p.Thr138Thr	synonymous	Exon 6 of 11	ENSP00000577865.1
	ROGDI	ENST00000912071.1		c.414G>A	p.Thr138Thr	synonymous	Exon 6 of 11	ENSP00000582130.1

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16660 AN: 152090 Hom.: 1159 Cov.: 33

Gnomad AFR AF: 0.0387

Gnomad AMI AF: 0.128

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.0360

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.133

GnomAD2 exomes AF: 0.130 AC: 32330 AN: 249506 AF XY: 0.137

Gnomad AFR exome AF: 0.0327

Gnomad AMR exome AF: 0.0779

Gnomad ASJ exome AF: 0.249

Gnomad EAS exome AF: 0.0299

Gnomad FIN exome AF: 0.121

Gnomad NFE exome AF: 0.144

Gnomad OTH exome AF: 0.144

GnomAD4 exome AF: 0.140 AC: 204537 AN: 1460210 Hom.: 15370 Cov.: 31 AF XY: 0.143 AC XY: 103590 AN XY: 726400

African (AFR) AF: 0.0334 AC: 1117 AN: 33462

American (AMR) AF: 0.0832 AC: 3712 AN: 44622

Ashkenazi Jewish (ASJ) AF: 0.244 AC: 6364 AN: 26068

East Asian (EAS) AF: 0.0521 AC: 2066 AN: 39674

South Asian (SAS) AF: 0.204 AC: 17541 AN: 86086

European-Finnish (FIN) AF: 0.125 AC: 6660 AN: 53362

Middle Eastern (MID) AF: 0.180 AC: 1038 AN: 5760

European-Non Finnish (NFE) AF: 0.141 AC: 157180 AN: 1110858

Other (OTH) AF: 0.147 AC: 8859 AN: 60318

GnomAD4 genome AF: 0.109 AC: 16633 AN: 152208 Hom.: 1153 Cov.: 33 AF XY: 0.109 AC XY: 8093 AN XY: 74418

African (AFR) AF: 0.0385 AC: 1599 AN: 41526

American (AMR) AF: 0.106 AC: 1620 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.243 AC: 843 AN: 3468

East Asian (EAS) AF: 0.0359 AC: 186 AN: 5184

South Asian (SAS) AF: 0.200 AC: 964 AN: 4826

European-Finnish (FIN) AF: 0.116 AC: 1225 AN: 10604

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.143 AC: 9738 AN: 67998

Other (OTH) AF: 0.132 AC: 278 AN: 2108

Alfa AF: 0.134 Hom.: 1687

Bravo AF: 0.104

Asia WGS AF: 0.127 AC: 441 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	Amelocerebrohypohidrotic syndrome (2)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.064
DANN	Benign	0.88
PhyloP100		-4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=98/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs11553876; hg19: chr16-4849705; COSMIC: COSV58927157; COSMIC: COSV58927157;