NM_024589.3:c.*292C>T

Variant names:

• chr16-4797168-G-A
• rs8118
• NM_024589.3:c.*292C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.544
• Publications: 16 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 -20 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_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
ROGDI	NM_024589.3	c.*292C>T		3_prime_UTR_variant	Exon 11 of 11	ENST00000322048.12	NP_078865.1
ROGDI	NR_046480.2	n.1163C>T		non_coding_transcript_exon_variant	Exon 10 of 10
ROGDI	XM_006720947.5	c.*292C>T		3_prime_UTR_variant	Exon 11 of 11		XP_006721010.1
ROGDI	XM_047434636.1	c.*292C>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.*292C>T		3_prime_UTR_variant	Exon 11 of 11	1	NM_024589.3	ENSP00000322832.6

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

African (AFR) AF: 0.225 AC: 1522 AN: 6762

American (AMR) AF: 0.540 AC: 3987 AN: 7386

Ashkenazi Jewish (ASJ) AF: 0.466 AC: 3123 AN: 6704

East Asian (EAS) AF: 0.325 AC: 4615 AN: 14216

South Asian (SAS) AF: 0.484 AC: 11189 AN: 23098

European-Finnish (FIN) AF: 0.413 AC: 5096 AN: 12334

Middle Eastern (MID) AF: 0.398 AC: 381 AN: 958

European-Non Finnish (NFE) AF: 0.454 AC: 58676 AN: 129162

Other (OTH) AF: 0.439 AC: 5553 AN: 12642

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

African (AFR) AF: 0.247 AC: 10216 AN: 41384

American (AMR) AF: 0.516 AC: 7870 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.489 AC: 1697 AN: 3470

East Asian (EAS) AF: 0.343 AC: 1763 AN: 5134

South Asian (SAS) AF: 0.496 AC: 2387 AN: 4810

European-Finnish (FIN) AF: 0.445 AC: 4704 AN: 10580

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.475 AC: 32236 AN: 67868

Other (OTH) AF: 0.442 AC: 934 AN: 2114

Alfa AF: 0.463 Hom.: 17979

Bravo AF: 0.408

Asia WGS AF: 0.476 AC: 1655 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Amelocerebrohypohidrotic syndrome Benign:1

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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
PhyloP100		0.54
Mutation Taster		=100/0	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: rs8118; hg19: chr16-4847169;