Genetic Variant ROGDI:c.822+8C>A (chr16-4797706-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_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

Variant links:

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 links:

ENSG00000285952 (HGNC:):

ENSG00000285952 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10264018).

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ROGDI	NM_024589.3 link	c.822+8C>A	splice_region_variant, intron_variant	Intron 10 of 10	ENST00000322048.12	NP_078865.1	Q9GZN7
ROGDI	XM_006720947.5 link	c.843+8C>A	splice_region_variant, intron_variant	Intron 10 of 10		XP_006721010.1
ROGDI	XM_047434636.1 link	c.573+8C>A	splice_region_variant, intron_variant	Intron 8 of 8		XP_047290592.1
ROGDI	NR_046480.2 link	n.829+8C>A	splice_region_variant, intron_variant	Intron 9 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ROGDI	ENST00000322048.12 link	c.822+8C>A		splice_region_variant, intron_variant	Intron 10 of 10	1	NM_024589.3	ENSP00000322832.6		Q9GZN7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

8.47e-7

AC:

AN:

1181046

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

580438

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000106

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Benign

0.021

DANN

Benign

0.45

DEOGEN2

Benign

0.0053

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.20

MetaRNN

Benign

0.10

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over