16-4800560-G-C

Position:

• chr16-4800560-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024589.3(ROGDI):​c.274C>G​(p.Pro92Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ROGDI NM_024589.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.77

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 (HGNC:):

ACMG classification

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=0.078362614).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ROGDI	NM_024589.3	c.274C>G	p.Pro92Ala	missense_variant	5/11	ENST00000322048.12	NP_078865.1
ROGDI	XM_006720947.5	c.274C>G	p.Pro92Ala	missense_variant	5/11		XP_006721010.1
ROGDI	XM_047434636.1	c.4C>G	p.Pro2Ala	missense_variant	3/9		XP_047290592.1
ROGDI	NR_046480.2	n.281C>G		non_coding_transcript_exon_variant	4/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ROGDI	ENST00000322048.12	c.274C>G	p.Pro92Ala	missense_variant	5/11	1	NM_024589.3	ENSP00000322832.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	12
DANN	Benign	0.64
DEOGEN2	Benign	0.16	T;T;T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.83	T;T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.078	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L;.;.
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.9	N;.;.
REVEL	Benign	0.064
Sift	Benign	0.86	T;.;.
Sift4G	Benign	0.65	T;.;T
Polyphen		0.0	B;.;.
Vest4		0.37
MutPred		0.27		Loss of ubiquitination at K90 (P = 0.0665);.;.;
MVP		0.081
MPC		0.022
ClinPred		0.084	T
GERP RS		2.3
Varity_R		0.066
gMVP		0.16

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-4850561;