16-4797344-G-A

Variant names:

• chr16-4797344-G-A
• rs78649123
• NM_024589.3:c.*116C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_024589.3(ROGDI):​c.*116C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000967 in 863,160 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0035 (5 hom., cov: 33)
  • Exomes 𝑓: 0.00042 (3 hom.)
• Consequence: ROGDI NM_024589.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.146
• Publications: 0 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 16-4797344-G-A is Benign according to our data. Variant chr16-4797344-G-A is described in ClinVar as [Benign]. Clinvar id is 2646159.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0035 (533/152350) while in subpopulation AFR AF = 0.012 (499/41582). AF 95% confidence interval is 0.0111. There are 5 homozygotes in GnomAd4. There are 248 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ROGDI	NM_024589.3	c.*116C>T		3_prime_UTR_variant	Exon 11 of 11	ENST00000322048.12	NP_078865.1
ROGDI	NR_046480.2	n.987C>T		non_coding_transcript_exon_variant	Exon 10 of 10
ROGDI	XM_006720947.5	c.*116C>T		3_prime_UTR_variant	Exon 11 of 11		XP_006721010.1
ROGDI	XM_047434636.1	c.*116C>T		3_prime_UTR_variant	Exon 9 of 9		XP_047290592.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ROGDI	ENST00000322048.12	c.*116C>T		3_prime_UTR_variant	Exon 11 of 11	1	NM_024589.3	ENSP00000322832.6

Frequencies

GnomAD3 genomes AF: 0.00346 AC: 526 AN: 152232 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.0119

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00177

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: 0.0000147

Gnomad OTH AF: 0.00287

GnomAD4 exome AF: 0.000425 AC: 302 AN: 710810 Hom.: 3 Cov.: 9 AF XY: 0.000376 AC XY: 138 AN XY: 367160

African (AFR) AF: 0.0132 AC: 237 AN: 17916

American (AMR) AF: 0.000895 AC: 21 AN: 23474

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15486

East Asian (EAS) AF: 0.00 AC: 0 AN: 34114

South Asian (SAS) AF: 0.00 AC: 0 AN: 53964

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45042

Middle Eastern (MID) AF: 0.00147 AC: 4 AN: 2712

European-Non Finnish (NFE) AF: 0.00000827 AC: 4 AN: 483644

Other (OTH) AF: 0.00104 AC: 36 AN: 34458

GnomAD4 genome AF: 0.00350 AC: 533 AN: 152350 Hom.: 5 Cov.: 33 AF XY: 0.00333 AC XY: 248 AN XY: 74498

African (AFR) AF: 0.0120 AC: 499 AN: 41582

American (AMR) AF: 0.00176 AC: 27 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68030

Other (OTH) AF: 0.00284 AC: 6 AN: 2116

Alfa AF: 0.00416 Hom.: 1

Bravo AF: 0.00417

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Feb 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ROGDI: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.2
DANN	Benign	0.33
PhyloP100		-0.15
Mutation Taster		=100/0	polymorphism

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: rs78649123; hg19: chr16-4847345;