rs201931071

Positions:

• chr16-4798142-C-G
• chr16-4798142-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_024589.3(ROGDI):​c.574G>C​(p.Val192Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,730 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V192I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ROGDI NM_024589.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.49

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35756245).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ROGDI	NM_024589.3	c.574G>C	p.Val192Leu	missense_variant	8/11	ENST00000322048.12
ROGDI	XM_006720947.5	c.574G>C	p.Val192Leu	missense_variant	8/11
ROGDI	XM_047434636.1	c.304G>C	p.Val102Leu	missense_variant	6/9
ROGDI	NR_046480.2	n.581G>C		non_coding_transcript_exon_variant	7/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ROGDI	ENST00000322048.12	c.574G>C	p.Val192Leu	missense_variant	8/11	1	NM_024589.3	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461730 Hom.: 0 Cov.: 36 AF XY: 0.00000138 AC XY: 1 AN XY: 727188

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.049	T;T;T;T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.11
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.89	D;D;D;D
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.36	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N;.;.;.
MutationTaster	Benign	0.96	D
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	0.57	N;.;.;.
REVEL	Benign	0.11
Sift	Uncertain	0.012	D;.;.;.
Sift4G	Benign	0.11	T;.;.;T
Polyphen		0.020	B;.;.;.
Vest4		0.58
MutPred		0.54		Loss of sheet (P = 0.0315);.;.;.;
MVP		0.085
MPC		0.026
ClinPred		0.92	D
GERP RS		3.6
Varity_R		0.36
gMVP		0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs201931071; hg19: chr16-4848143;