chr16-4797706-G-T

Variant names:

• chr16-4797706-G-T
• rs376868221
• NM_024589.3:c.822+8C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024589.3(ROGDI):​c.822+8C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000847 in 1,181,046 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 8.5e-7 (0 hom.)
• Consequence: ROGDI NM_024589.3 splice_region, intron
• Scores: Splicing: ADA: 0.0001810
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.03
• 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)

ENSG00000285952 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10264018).

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.822+8C>A		splice_region intron	N/A	NP_078865.1
	ROGDI	NR_046480.2		n.829+8C>A		splice_region intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROGDI	ENST00000322048.12	TSL:1 MANE Select	c.822+8C>A		splice_region intron	N/A	ENSP00000322832.6
	ROGDI	ENST00000591392.5	TSL:3	c.758C>A	p.Pro253Gln	missense	Exon 9 of 9	ENSP00000467509.1
	ROGDI	ENST00000586504.5	TSL:5	c.550+8C>A		splice_region intron	N/A	ENSP00000465076.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 8.47e-7 AC: 1 AN: 1181046 Hom.: 0 Cov.: 37 AF XY: 0.00 AC XY: 0 AN XY: 580438

African (AFR) AF: 0.00 AC: 0 AN: 24660

American (AMR) AF: 0.00 AC: 0 AN: 31670

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17232

East Asian (EAS) AF: 0.00 AC: 0 AN: 23880

South Asian (SAS) AF: 0.00 AC: 0 AN: 59334

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34320

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4462

European-Non Finnish (NFE) AF: 0.00000106 AC: 1 AN: 942052

Other (OTH) AF: 0.00 AC: 0 AN: 43436

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	0.021
DANN	Benign	0.45
DEOGEN2	Benign	0.0053	T
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.20	T
MetaRNN	Benign	0.10	T
PhyloP100		-3.0
MVP		0.10
GERP RS		-6.8

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00018
dbscSNV1_RF	Benign	0.058
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: rs376868221; hg19: chr16-4847707;