ROGDI p.Asp147Glu

Variant names:

• chr16-4798659-G-T
• NM_024589.3:c.441C>A
• ROGDI p.Asp147Glu

Your query was ambiguous. Multiple possible variants found:

• chr16-4798659-G-T
• chr16-4798659-G-C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_024589.3(ROGDI):​c.441C>A​(p.Asp147Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. D147D) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ROGDI NM_024589.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.380
• Publications: 0 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: PanelApp Australia, G2P, Orphanet, ClinGen, Labcorp Genetics (formerly Invitae)

ENSG00000285952 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024589.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROGDI	NM_024589.3	MANE Select	c.441C>A	p.Asp147Glu	missense	Exon 7 of 11	NP_078865.1	Q9GZN7
	ROGDI	NR_046480.2		n.448C>A		non_coding_transcript_exon	Exon 6 of 10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROGDI	ENST00000322048.12	TSL:1 MANE Select	c.441C>A	p.Asp147Glu	missense	Exon 7 of 11	ENSP00000322832.6	Q9GZN7
	ROGDI	ENST00000907806.1		c.441C>A	p.Asp147Glu	missense	Exon 7 of 11	ENSP00000577865.1
	ROGDI	ENST00000912071.1		c.441C>A	p.Asp147Glu	missense	Exon 7 of 11	ENSP00000582130.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1413028 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 698728

African (AFR) AF: 0.00 AC: 0 AN: 33078

American (AMR) AF: 0.00 AC: 0 AN: 36746

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25246

East Asian (EAS) AF: 0.00 AC: 0 AN: 38306

South Asian (SAS) AF: 0.00 AC: 0 AN: 80546

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5714

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1090122

Other (OTH) AF: 0.00 AC: 0 AN: 58854

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.83
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	0.58
DANN	Uncertain	0.98
DEOGEN2	Benign	0.058	T
Eigen	Benign	-0.91
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.40	N
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.027	D
MetaRNN	Uncertain	0.52	D
MetaSVM	Benign	-0.72	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		-0.38
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	-1.5	N
REVEL	Uncertain	0.33
Sift	Benign	0.071	T
Sift4G	Benign	0.23	T
Varity_R		0.35
gMVP		0.43

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr16-4848660;