16-4797840-G-T

Variant names:

• chr16-4797840-G-T
• NM_024589.3:c.696C>A

Variant summary

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

The NM_024589.3(ROGDI):​c.696C>A​(p.Phe232Leu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,788 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. F232F) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ROGDI NM_024589.3 missense, splice_region
• Scores: Splicing: ADA: 0.00001435
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.141

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.888

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ROGDI	NM_024589.3	c.696C>A	p.Phe232Leu	missense_variant, splice_region_variant	Exon 10 of 11	ENST00000322048.12	NP_078865.1
ROGDI	XM_006720947.5	c.717C>A	p.Ser239Arg	missense_variant	Exon 10 of 11		XP_006721010.1
ROGDI	XM_047434636.1	c.447C>A	p.Ser149Arg	missense_variant	Exon 8 of 9		XP_047290592.1
ROGDI	NR_046480.2	n.703C>A		splice_region_variant, non_coding_transcript_exon_variant	Exon 9 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ROGDI	ENST00000322048.12	c.696C>A	p.Phe232Leu	missense_variant, splice_region_variant	Exon 10 of 11	1	NM_024589.3	ENSP00000322832.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458788 Hom.: 0 Cov.: 37 AF XY: 0.00000138 AC XY: 1 AN XY: 725840

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: 8.99e-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	0.93
BayesDel_addAF	Uncertain	0.042	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	13
DANN	Uncertain	0.98
DEOGEN2	Benign	0.059	T;T;T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.70	D
LIST_S2	Uncertain	0.89	D;D;D
M_CAP	Benign	0.027	D
MetaRNN	Pathogenic	0.89	D;D;D
MetaSVM	Benign	-0.82	T
MutationAssessor	Uncertain	2.0	M;.;.
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-1.3	N;.;.
REVEL	Uncertain	0.32
Sift	Benign	0.19	T;.;.
Sift4G	Pathogenic	0.0	D;.;.
Polyphen		0.99	D;.;.
Vest4		0.93
MutPred		0.86		Gain of disorder (P = 0.1403);.;.;
MVP		0.23
MPC		0.056
ClinPred		0.92	D
GERP RS		-3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9
Varity_R		0.27
gMVP		0.77

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000014
dbscSNV1_RF	Benign	0.012
SpliceAI score (max)		0.45		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.45		Position offset: -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: chr16-4847841;