16-4797168-G-A

Position:

• chr16-4797168-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_024589.3(ROGDI):​c.*292C>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 0.428 in 365,080 control chromosomes in the GnomAD database, including 35,247 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.41 (13638 hom., cov: 31)
  • Exomes 𝑓: 0.44 (21609 hom.)
• Consequence: ROGDI NM_024589.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.544

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 16-4797168-G-A is Benign according to our data. Variant chr16-4797168-G-A is described in ClinVar as [Benign]. Clinvar id is 319394.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.506 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ROGDI	NM_024589.3	c.*292C>T		3_prime_UTR_variant	11/11	ENST00000322048.12
ROGDI	XM_006720947.5	c.*292C>T		3_prime_UTR_variant	11/11
ROGDI	XM_047434636.1	c.*292C>T		3_prime_UTR_variant	9/9
ROGDI	NR_046480.2	n.1163C>T		non_coding_transcript_exon_variant	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ROGDI	ENST00000322048.12	c.*292C>T		3_prime_UTR_variant	11/11	1	NM_024589.3	P1
ROGDI	ENST00000591292.5	n.2485C>T		non_coding_transcript_exon_variant	7/7	2
ROGDI	ENST00000587377.5	c.*476C>T		3_prime_UTR_variant, NMD_transcript_variant	11/11	5
ROGDI	ENST00000587843.5	c.*894C>T		3_prime_UTR_variant, NMD_transcript_variant	10/10	2

Frequencies

GnomAD3 genomes AF: 0.410 AC: 62251 AN: 151700 Hom.: 13628 Cov.: 31

Gnomad AFR AF: 0.247

Gnomad AMI AF: 0.387

Gnomad AMR AF: 0.515

Gnomad ASJ AF: 0.489

Gnomad EAS AF: 0.344

Gnomad SAS AF: 0.498

Gnomad FIN AF: 0.445

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.475

Gnomad OTH AF: 0.436

GnomAD4 exome AF: 0.441 AC: 94142 AN: 213262 Hom.: 21609 Cov.: 0 AF XY: 0.447 AC XY: 50019 AN XY: 111876

Gnomad4 AFR exome AF: 0.225

Gnomad4 AMR exome AF: 0.540

Gnomad4 ASJ exome AF: 0.466

Gnomad4 EAS exome AF: 0.325

Gnomad4 SAS exome AF: 0.484

Gnomad4 FIN exome AF: 0.413

Gnomad4 NFE exome AF: 0.454

Gnomad4 OTH exome AF: 0.439

GnomAD4 genome AF: 0.410 AC: 62283 AN: 151818 Hom.: 13638 Cov.: 31 AF XY: 0.413 AC XY: 30603 AN XY: 74184

Gnomad4 AFR AF: 0.247

Gnomad4 AMR AF: 0.516

Gnomad4 ASJ AF: 0.489

Gnomad4 EAS AF: 0.343

Gnomad4 SAS AF: 0.496

Gnomad4 FIN AF: 0.445

Gnomad4 NFE AF: 0.475

Gnomad4 OTH AF: 0.442

Alfa AF: 0.465 Hom.: 15741

Bravo AF: 0.408

Asia WGS AF: 0.476 AC: 1655 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Amelocerebrohypohidrotic syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	12
DANN	Benign	0.84

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

Publications

LitVar

Other links and lift over

dbSNP: rs8118; hg19: chr16-4847169;