chr16-4797190-A-G

Variant names:

• chr16-4797190-A-G
• rs76192577
• NM_024589.3:c.*270T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BS1 BS2

The NM_024589.3(ROGDI):​c.*270T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00257 in 425,784 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0060 (5 hom., cov: 33)
  • Exomes 𝑓: 0.00068 (0 hom.)
• Consequence: ROGDI NM_024589.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.574
• 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: PanelApp Australia, G2P, Orphanet, ClinGen, Labcorp Genetics (formerly Invitae)

ENSG00000285952 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.26).
• BP6: Variant 16-4797190-A-G is Benign according to our data. Variant chr16-4797190-A-G is described in ClinVar as Benign. ClinVar VariationId is 319395.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00597 (908/152142) while in subpopulation AFR AF = 0.0209 (866/41492). AF 95% confidence interval is 0.0197. There are 5 homozygotes in GnomAd4. There are 437 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

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.*270T>C		3_prime_UTR	Exon 11 of 11	NP_078865.1	Q9GZN7
	ROGDI	NR_046480.2		n.1141T>C		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.*270T>C		3_prime_UTR	Exon 11 of 11	ENSP00000322832.6	Q9GZN7
	ROGDI	ENST00000907806.1		c.*270T>C		3_prime_UTR	Exon 11 of 11	ENSP00000577865.1
	ROGDI	ENST00000912071.1		c.*270T>C		3_prime_UTR	Exon 11 of 11	ENSP00000582130.1

Frequencies

GnomAD3 genomes AF: 0.00588 AC: 894 AN: 152024 Hom.: 5 Cov.: 33

Gnomad AFR AF: 0.0206

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00183

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: 0.00621

GnomAD4 exome AF: 0.000676 AC: 185 AN: 273642 Hom.: 0 Cov.: 0 AF XY: 0.000632 AC XY: 91 AN XY: 144070

African (AFR) AF: 0.0178 AC: 147 AN: 8272

American (AMR) AF: 0.00143 AC: 13 AN: 9074

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8688

East Asian (EAS) AF: 0.00 AC: 0 AN: 18692

South Asian (SAS) AF: 0.0000683 AC: 2 AN: 29264

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 16850

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1212

European-Non Finnish (NFE) AF: 0.0000302 AC: 5 AN: 165578

Other (OTH) AF: 0.00112 AC: 18 AN: 16012

GnomAD4 genome AF: 0.00597 AC: 908 AN: 152142 Hom.: 5 Cov.: 33 AF XY: 0.00588 AC XY: 437 AN XY: 74378

African (AFR) AF: 0.0209 AC: 866 AN: 41492

American (AMR) AF: 0.00183 AC: 28 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67962

Other (OTH) AF: 0.00615 AC: 13 AN: 2114

Alfa AF: 0.000382 Hom.: 0

Bravo AF: 0.00679

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Amelocerebrohypohidrotic syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.26
CADD	Benign	14
DANN	Benign	0.81
PhyloP100		0.57
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: rs76192577; hg19: chr16-4847191;