Variant 11-200020-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_053280.5(ODF3):c.752T>C(p.Val251Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000703 in 1,613,870 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: 𝑓 0.00039 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00074 ( 0 hom. )

Consequence

ODF3
NM_053280.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.30

Variant links:

Genes affected

ODF3 (HGNC:):

ODF3 links:

CIMAP1A (HGNC:19905): (ciliary microtubule associated protein 1A) ODF3 is a component of sperm flagella outer dense fibers, which add stiffness, elastic recoil, and protection against shearing forces during sperm movement.[supplied by OMIM, Apr 2004]

CIMAP1A links:

BET1L (HGNC:19348): (Bet1 golgi vesicular membrane trafficking protein like) Enables SNAP receptor activity. Involved in regulation of retrograde vesicle-mediated transport, Golgi to ER and retrograde transport, endosome to Golgi. Located in Golgi apparatus and endosome. Implicated in uterine fibroid. Biomarker of endometrial adenocarcinoma. [provided by Alliance of Genome Resources, Apr 2022]

BET1L links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.1375629).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ODF3	NM_053280.5 linkuse as main transcript	c.752T>C	p.Val251Ala	missense_variant	7/7	ENST00000325113.9
ODF3	NM_001286136.2 linkuse as main transcript	c.611T>C	p.Val204Ala	missense_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CIMAP1A	ENST00000325113.9 linkuse as main transcript	c.752T>C	p.Val251Ala	missense_variant	7/7	1	NM_053280.5	P1	Q96PU9-1
CIMAP1A	ENST00000525282.1 linkuse as main transcript	c.611T>C	p.Val204Ala	missense_variant	6/6	1			Q96PU9-3
BET1L	ENST00000410108.5 linkuse as main transcript	c.168+5591A>G		intron_variant		3
CIMAP1A	ENST00000531679.1 linkuse as main transcript	n.2812T>C		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes

AF:

0.000388

AC:

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000735

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.000299

AC:

AN:

250562

Hom.:

AF XY:

0.000325

AC XY:

AN XY:

135544

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.0000289

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:

0.000620

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000735

AC:

1075

AN:

1461682

Hom.:

Cov.:

AF XY:

0.000712

AC XY:

518

AN XY:

727122

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000131

Gnomad4 NFE exome

AF:

0.000920

Gnomad4 OTH exome

AF:

0.000679

GnomAD4 genome

AF:

0.000388

AC:

AN:

152188

Hom.:

Cov.:

AF XY:

0.000282

AC XY:

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.000735

Gnomad4 OTH

AF:

0.000955

Alfa

AF:

0.000682

Hom.:

Bravo

AF:

0.000378

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.000321

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000872

EpiControl

AF:

0.000533

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

Aug 10, 2021

The c.752T>C (p.V251A) alteration is located in exon 7 (coding exon 6) of the ODF3 gene. This alteration results from a T to C substitution at nucleotide position 752, causing the valine (V) at amino acid position 251 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

0.16

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.14

T;.;.

Eigen

Benign

-0.11

Eigen_PC

Benign

-0.041

FATHMM_MKL

Benign

0.59

LIST_S2

Benign

0.64

T;T;T

M_CAP

Benign

0.018

MetaRNN

Benign

0.14

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

L;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-2.1

N;N;.

REVEL

Benign

0.17

Sift

Uncertain

0.012

D;D;.

Sift4G

Uncertain

0.012

D;D;D

Polyphen

0.38

B;.;.

Vest4

0.52

MVP

0.19

MPC

0.26

ClinPred

0.055

GERP RS

5.0

Varity_R

0.12

gMVP

0.61

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