Variant 19-464254-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_182577.3(CIMAP1D):c.460C>A(p.Leu154Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000145 in 1,382,154 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 (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CIMAP1D
NM_182577.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0560

Variant links:

Genes affected

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

CIMAP1D links:

ODF3L2 (HGNC:):

ODF3L2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05947128).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CIMAP1D	NM_182577.3 linkuse as main transcript	c.460C>A	p.Leu154Met	missense_variant	4/4	ENST00000315489.5	NP_872383.1	Q3SX64-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ODF3L2	ENST00000315489.5 linkuse as main transcript	c.460C>A	p.Leu154Met	missense_variant	4/4	1	NM_182577.3	ENSP00000318029.2	Q3SX64-1
ODF3L2	ENST00000382696.7 linkuse as main transcript	c.352C>A	p.Leu118Met	missense_variant	3/3	1		ENSP00000372143.2	Q3SX64-2
ODF3L2	ENST00000591681.3 linkuse as main transcript	n.447C>A		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000753

AC:

AN:

132806

Hom.:

AF XY:

0.0000139

AC XY:

AN XY:

71876

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000203

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000145

AC:

AN:

1382154

Hom.:

Cov.:

AF XY:

0.00000293

AC XY:

AN XY:

682106

show subpopulations

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:

0.00000186

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jul 17, 2023

The c.460C>A (p.L154M) alteration is located in exon 4 (coding exon 4) of the ODF3L2 gene. This alteration results from a C to A substitution at nucleotide position 460, causing the leucine (L) at amino acid position 154 to be replaced by a methionine (M). 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

0.094

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.71

DEOGEN2

Benign

0.0079

.;T

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.092

LIST_S2

Benign

0.56

T;T

M_CAP

Benign

0.042

MetaRNN

Benign

0.059

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.81

.;L

PrimateAI

Uncertain

0.52

PROVEAN

Benign

0.25

N;N

REVEL

Benign

0.026

Sift

Benign

0.22

T;T

Sift4G

Benign

0.23

T;T

Polyphen

0.065

B;B

Vest4

0.14

MutPred

0.20

.;Loss of phosphorylation at T156 (P = 0.0811);

MVP

0.081

MPC

0.40

ClinPred

0.052

GERP RS

3.4

Varity_R

0.10

gMVP

0.22

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