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, Labcorp Genetics (formerly Invitae), ClinGen

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 VariationId 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.

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.*380G>A		3_prime_UTR	Exon 11 of 11	NP_078865.1	Q9GZN7
	ROGDI	NR_046480.2		n.1251G>A		non_coding_transcript_exon	Exon 10 of 10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROGDI	ENST00000322048.12	TSL:1 MANE Select	c.*380G>A		3_prime_UTR	Exon 11 of 11	ENSP00000322832.6	Q9GZN7
	ROGDI	ENST00000907806.1		c.*380G>A		3_prime_UTR	Exon 11 of 11	ENSP00000577865.1
	ROGDI	ENST00000912071.1		c.*380G>A		3_prime_UTR	Exon 11 of 11	ENSP00000582130.1

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

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Amelocerebrohypohidrotic syndrome (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

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;