rs1060502982

Positions:

• chr16-4799771-G-A
• chr16-4799771-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_024589.3(ROGDI):​c.347C>T​(p.Ala116Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,914 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ROGDI NM_024589.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.96

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.916

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ROGDI	NM_024589.3	c.347C>T	p.Ala116Val	missense_variant	6/11	ENST00000322048.12	NP_078865.1
ROGDI	XM_006720947.5	c.347C>T	p.Ala116Val	missense_variant	6/11		XP_006721010.1
ROGDI	XM_047434636.1	c.77C>T	p.Ala26Val	missense_variant	4/9		XP_047290592.1
ROGDI	NR_046480.2	n.354C>T		non_coding_transcript_exon_variant	5/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ROGDI	ENST00000322048.12	c.347C>T	p.Ala116Val	missense_variant	6/11	1	NM_024589.3	ENSP00000322832	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000400 AC: 1 AN: 250172 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135316

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460914 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726742

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

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: 9.00e-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	Pathogenic	0.87
BayesDel_addAF	Uncertain	0.070	D
BayesDel_noAF	Benign	-0.14
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T;T;T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D;D;D
M_CAP	Benign	0.061	D
MetaRNN	Pathogenic	0.92	D;D;D
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.2	M;.;.
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-2.8	D;.;.
REVEL	Benign	0.25
Sift	Benign	0.093	T;.;.
Sift4G	Uncertain	0.018	D;.;D
Polyphen		0.57	P;.;.
Vest4		0.81
MutPred		0.86		Loss of disorder (P = 0.1236);.;.;
MVP		0.38
MPC		0.085
ClinPred		0.89	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.63
gMVP		0.49

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: rs1060502982; hg19: chr16-4849772;