rs3210637

Variant names:

• chr16-4797080-C-T
• rs3210637
• NM_024589.3:c.*380G>A

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.*380G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0429 in 244,836 control chromosomes in the GnomAD database, including 232 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.045 (146 hom., cov: 32)
  • Exomes 𝑓: 0.039 (86 hom.)
• Consequence: ROGDI NM_024589.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.23
• Publications: 2 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=-0.83).
• BP6: Variant 16-4797080-C-T is Benign according to our data. Variant chr16-4797080-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 319391.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0529 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ROGDI	NM_024589.3	c.*380G>A		3_prime_UTR_variant	Exon 11 of 11	ENST00000322048.12	NP_078865.1
ROGDI	NR_046480.2	n.1251G>A		non_coding_transcript_exon_variant	Exon 10 of 10
ROGDI	XM_006720947.5	c.*380G>A		3_prime_UTR_variant	Exon 11 of 11		XP_006721010.1
ROGDI	XM_047434636.1	c.*380G>A		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.*380G>A		3_prime_UTR_variant	Exon 11 of 11	1	NM_024589.3	ENSP00000322832.6

Frequencies

GnomAD3 genomes AF: 0.0454 AC: 6908 AN: 152134 Hom.: 146 Cov.: 32

Gnomad AFR AF: 0.0396

Gnomad AMI AF: 0.0493

Gnomad AMR AF: 0.0418

Gnomad ASJ AF: 0.0360

Gnomad EAS AF: 0.00558

Gnomad SAS AF: 0.0464

Gnomad FIN AF: 0.0365

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0544

Gnomad OTH AF: 0.0473

GnomAD4 exome AF: 0.0389 AC: 3598 AN: 92584 Hom.: 86 Cov.: 0 AF XY: 0.0387 AC XY: 1886 AN XY: 48698

African (AFR) AF: 0.0253 AC: 87 AN: 3436

American (AMR) AF: 0.0378 AC: 169 AN: 4466

Ashkenazi Jewish (ASJ) AF: 0.0364 AC: 87 AN: 2388

East Asian (EAS) AF: 0.00377 AC: 20 AN: 5302

South Asian (SAS) AF: 0.0402 AC: 479 AN: 11916

European-Finnish (FIN) AF: 0.0257 AC: 93 AN: 3624

Middle Eastern (MID) AF: 0.0320 AC: 13 AN: 406

European-Non Finnish (NFE) AF: 0.0439 AC: 2460 AN: 56038

Other (OTH) AF: 0.0379 AC: 190 AN: 5008

GnomAD4 genome AF: 0.0454 AC: 6905 AN: 152252 Hom.: 146 Cov.: 32 AF XY: 0.0448 AC XY: 3336 AN XY: 74446

African (AFR) AF: 0.0395 AC: 1642 AN: 41548

American (AMR) AF: 0.0417 AC: 638 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0360 AC: 125 AN: 3470

East Asian (EAS) AF: 0.00559 AC: 29 AN: 5188

South Asian (SAS) AF: 0.0460 AC: 222 AN: 4828

European-Finnish (FIN) AF: 0.0365 AC: 388 AN: 10618

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0544 AC: 3698 AN: 67988

Other (OTH) AF: 0.0468 AC: 99 AN: 2114

Alfa AF: 0.0495 Hom.: 93

Bravo AF: 0.0457

Asia WGS AF: 0.0310 AC: 108 AN: 3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Amelocerebrohypohidrotic syndrome Benign:1

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance: Likely 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 allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.1
DANN	Benign	0.47
PhyloP100		-1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs3210637; hg19: chr16-4847081;