Variant 19-464143-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_182577.3(ODF3L2):c.571C>G(p.Pro191Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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. P191R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000041 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00012 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ODF3L2
NM_182577.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.207

Variant links:

Genes affected

ODF3L2 (HGNC:):

ODF3L2 links:

CIMAP1D (HGNC:26841): (CIMAP1 family member D) Located in cytoplasmic microtubule. [provided by Alliance of Genome Resources, Apr 2022]

CIMAP1D links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005506903).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ODF3L2	NM_182577.3 linkuse as main transcript	c.571C>G	p.Pro191Ala	missense_variant	4/4	ENST00000315489.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CIMAP1D	ENST00000315489.5 linkuse as main transcript	c.571C>G	p.Pro191Ala	missense_variant	4/4	1	NM_182577.3	P2	Q3SX64-1
CIMAP1D	ENST00000382696.7 linkuse as main transcript	c.463C>G	p.Pro155Ala	missense_variant	3/3	1		A2	Q3SX64-2
CIMAP1D	ENST00000591681.3 linkuse as main transcript			downstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

145398

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00133

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000845

AC:

AN:

82838

Hom.:

AF XY:

0.0000911

AC XY:

AN XY:

43928

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000342

Gnomad EAS exome

AF:

0.000734

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000118

AC:

AN:

407984

Hom.:

Cov.:

AF XY:

0.000115

AC XY:

AN XY:

216946

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000993

Gnomad4 EAS exome

AF:

0.00212

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000160

Gnomad4 OTH exome

AF:

0.0000990

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000412

AC:

AN:

145536

Hom.:

Cov.:

AF XY:

0.0000565

AC XY:

AN XY:

70816

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00133

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000871

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000237

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3472

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 26, 2023

The c.571C>G (p.P191A) 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 571, causing the proline (P) at amino acid position 191 to be replaced by an alanine (A). 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

0.056

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

Cadd

Benign

4.0

Dann

Benign

0.66

Eigen

Benign

-0.97

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.064

LIST_S2

Benign

0.65

T;T

M_CAP

Benign

0.034

MetaRNN

Benign

0.0055

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.48

PROVEAN

Benign

0.22

N;N

REVEL

Benign

0.032

Sift

Benign

0.57

T;T

Sift4G

Benign

0.77

T;T

Polyphen

0.026

B;B

Vest4

0.11

MutPred

0.17

.;Loss of glycosylation at P191 (P = 0.0135);

MVP

0.10

MPC

0.32

ClinPred

0.060

GERP RS

3.3

Varity_R

0.041

gMVP

0.24

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over