16-4800560-G-A

Position:

• chr16-4800560-G-A

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>T​(p.Pro92Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000706 in 1,415,878 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• 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]

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=0.070981175).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ROGDI	NM_024589.3	c.274C>T	p.Pro92Ser	missense_variant	5/11	ENST00000322048.12	NP_078865.1
ROGDI	XM_006720947.5	c.274C>T	p.Pro92Ser	missense_variant	5/11		XP_006721010.1
ROGDI	XM_047434636.1	c.4C>T	p.Pro2Ser	missense_variant	3/9		XP_047290592.1
ROGDI	NR_046480.2	n.281C>T		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>T	p.Pro92Ser	missense_variant	5/11	1	NM_024589.3	ENSP00000322832	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.0000111 AC: 2 AN: 180138 Hom.: 0 AF XY: 0.0000105 AC XY: 1 AN XY: 95566

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000373

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000612

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.06e-7 AC: 1 AN: 1415878 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 699682

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: 0.0000124

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

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	0.087
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	16
DANN	Benign	0.70
DEOGEN2	Benign	0.050	T;T;T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.62
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.76	T;T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.071	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L;.;.
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-1.3	N;.;.
REVEL	Benign	0.039
Sift	Benign	0.90	T;.;.
Sift4G	Benign	0.62	T;.;T
Polyphen		0.072	B;.;.
Vest4		0.35
MutPred		0.27		Gain of MoRF binding (P = 0.0695);.;.;
MVP		0.081
MPC		0.038
ClinPred		0.044	T
GERP RS		2.3
Varity_R		0.077
gMVP		0.26

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

LitVar

Other links and lift over

dbSNP: rs143620755; hg19: chr16-4850561;