16-4802372-G-C

Variant names:

• chr16-4802372-G-C
• rs113858060
• NM_024589.3:c.117+10C>G

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_024589.3(ROGDI):​c.117+10C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00169 in 1,566,318 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0018 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0017 (7 hom.)
• Consequence: ROGDI NM_024589.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.306
• Publications: 0 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)

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 16-4802372-G-C is Benign according to our data. Variant chr16-4802372-G-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 416245.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAdExome4 at 7 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROGDI	NM_024589.3	MANE Select	c.117+10C>G		intron	N/A	NP_078865.1
	ROGDI	NR_046480.2		n.179+10C>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROGDI	ENST00000322048.12	TSL:1 MANE Select	c.117+10C>G		intron	N/A	ENSP00000322832.6
	ROGDI	ENST00000592112.1	TSL:2	n.412C>G		non_coding_transcript_exon	Exon 2 of 2
	ROGDI	ENST00000591392.5	TSL:3	c.45+155C>G		intron	N/A	ENSP00000467509.1

Frequencies

GnomAD3 genomes AF: 0.00183 AC: 279 AN: 152124 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00316

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00204

Gnomad OTH AF: 0.000958

GnomAD2 exomes AF: 0.000741 AC: 132 AN: 178084 AF XY: 0.000673

Gnomad AFR exome AF: 0.00290

Gnomad AMR exome AF: 0.0000746

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000221

Gnomad NFE exome AF: 0.00117

Gnomad OTH exome AF: 0.00109

GnomAD4 exome AF: 0.00168 AC: 2372 AN: 1414076 Hom.: 7 Cov.: 31 AF XY: 0.00168 AC XY: 1178 AN XY: 701444

African (AFR) AF: 0.00322 AC: 102 AN: 31712

American (AMR) AF: 0.000133 AC: 5 AN: 37522

Ashkenazi Jewish (ASJ) AF: 0.0000408 AC: 1 AN: 24510

East Asian (EAS) AF: 0.00 AC: 0 AN: 37504

South Asian (SAS) AF: 0.00 AC: 0 AN: 80256

European-Finnish (FIN) AF: 0.000538 AC: 25 AN: 46430

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5584

European-Non Finnish (NFE) AF: 0.00199 AC: 2178 AN: 1092196

Other (OTH) AF: 0.00105 AC: 61 AN: 58362

GnomAD4 genome AF: 0.00183 AC: 279 AN: 152242 Hom.: 0 Cov.: 33 AF XY: 0.00161 AC XY: 120 AN XY: 74446

African (AFR) AF: 0.00315 AC: 131 AN: 41572

American (AMR) AF: 0.000261 AC: 4 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5160

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.000283 AC: 3 AN: 10596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00204 AC: 139 AN: 67996

Other (OTH) AF: 0.000948 AC: 2 AN: 2110

Alfa AF: 0.000542 Hom.: 0

Bravo AF: 0.00196

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)
-	-	3	Amelocerebrohypohidrotic syndrome (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.3
DANN	Benign	0.60
PhyloP100		-0.31
PromoterAI		0.029	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs113858060; hg19: chr16-4852373;