16-4799704-C-G

Variant names:

• chr16-4799704-C-G
• rs11553876
• NM_024589.3:c.414G>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_024589.3(ROGDI):​c.414G>C​(p.Thr138Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. T138T) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ROGDI NM_024589.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.74
• Publications: 13 publications found

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]

ROGDI Gene-Disease associations (from GenCC):

• amelocerebrohypohidrotic syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, ClinGen, Labcorp Genetics (formerly Invitae)

ENSG00000285952 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP7: Synonymous conserved (PhyloP=-4.74 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ROGDI	NM_024589.3	c.414G>C	p.Thr138Thr	synonymous_variant	Exon 6 of 11	ENST00000322048.12	NP_078865.1
ROGDI	XM_006720947.5	c.414G>C	p.Thr138Thr	synonymous_variant	Exon 6 of 11		XP_006721010.1
ROGDI	XM_047434636.1	c.144G>C	p.Thr48Thr	synonymous_variant	Exon 4 of 9		XP_047290592.1
ROGDI	NR_046480.2	n.421G>C		non_coding_transcript_exon_variant	Exon 5 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ROGDI	ENST00000322048.12	c.414G>C	p.Thr138Thr	synonymous_variant	Exon 6 of 11	1	NM_024589.3	ENSP00000322832.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.016
DANN	Benign	0.77
PhyloP100		-4.7

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

Other links and lift over

dbSNP: rs11553876; hg19: chr16-4849705;