19-464142-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_182577.3(ODF3L2):c.572C>G(p.Pro191Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000501 in 399,582 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. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P191A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000050 (0 hom.)
• Consequence: ODF3L2 NM_182577.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.19

Genes affected

ODF3L2 (HGNC:):

CIMAP1D (HGNC:26841): (CIMAP1 family member D) Located in cytoplasmic microtubule. [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=0.096309155).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ODF3L2	NM_182577.3	c.572C>G	p.Pro191Arg	missense_variant	4/4	ENST00000315489.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CIMAP1D	ENST00000315489.5	c.572C>G	p.Pro191Arg	missense_variant	4/4	1	NM_182577.3	P2
CIMAP1D	ENST00000382696.7	c.464C>G	p.Pro155Arg	missense_variant	3/3	1		A2
CIMAP1D	ENST00000591681.3			downstream_gene_variant		2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000501 AC: 2 AN: 399582 Hom.: 0 Cov.: 0 AF XY: 0.00000470 AC XY: 1 AN XY: 212832

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: 0.00000817

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 16, 2023

The c.572C>G (p.P191R) alteration is located in exon 4 (coding exon 4) of the ODF3L2 gene. This alteration results from a C to G substitution at nucleotide position 572, causing the proline (P) at amino acid position 191 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
Cadd	Benign	12
Dann	Benign	0.57
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.069	N
LIST_S2	Benign	0.72	T;T
M_CAP	Benign	0.055	D
MetaRNN	Benign	0.096	T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	N;N
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.83	N;N
REVEL	Benign	0.058
Sift	Benign	0.39	T;T
Sift4G	Benign	0.53	T;T
Polyphen		0.50	P;P
Vest4		0.17
MutPred		0.22		.;Loss of glycosylation at P191 (P = 0.0135);
MVP		0.22
MPC		0.42
ClinPred		0.28	T
GERP RS		0.86
Varity_R		0.040
gMVP		0.32

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-464142;