16-4801315-G-C

Variant names:

• chr16-4801315-G-C
• NM_024589.3:c.207C>G

Variant summary

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

The NM_024589.3(ROGDI):​c.207C>G​(p.Asp69Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,828 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ROGDI NM_024589.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.89

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]

ENSG00000285952 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ROGDI	NM_024589.3	c.207C>G	p.Asp69Glu	missense_variant	Exon 4 of 11	ENST00000322048.12	NP_078865.1
ROGDI	XM_006720947.5	c.207C>G	p.Asp69Glu	missense_variant	Exon 4 of 11		XP_006721010.1
ROGDI	XM_047434636.1	c.-16+188C>G		intron_variant	Intron 2 of 8		XP_047290592.1
ROGDI	NR_046480.2	n.262+188C>G		intron_variant	Intron 3 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ROGDI	ENST00000322048.12	c.207C>G	p.Asp69Glu	missense_variant	Exon 4 of 11	1	NM_024589.3	ENSP00000322832.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455828 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 723368

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: 9.03e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.026	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.059	T;T
Eigen	Benign	0.065
Eigen_PC	Benign	0.035
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Uncertain	0.090	D
MetaRNN	Uncertain	0.70	D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L;.
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-1.9	N;.
REVEL	Benign	0.26
Sift	Benign	0.24	T;.
Sift4G	Benign	0.39	T;.
Polyphen		1.0	D;.
Vest4		0.89
MutPred		0.81		Gain of solvent accessibility (P = 0.1014);.;
MVP		0.088
MPC		0.15
ClinPred		0.77	D
GERP RS		2.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.33
gMVP		0.26

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr16-4851316;