Variant chr8-102560808-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_024410.4(ODF1):c.677C>T(p.Pro226Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000193 in 854,824 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 21)

Exomes 𝑓: 0.00020 ( 0 hom. )

Consequence

ODF1
NM_024410.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.61

Variant links:

Genes affected

ODF1 (HGNC:8113): (outer dense fiber of sperm tails 1) The outer dense fibers are cytoskeletal structures that surround the axoneme in the middle piece and principal piece of the sperm tail. The fibers function in maintaining the elastic structure and recoil of the sperm tail as well as in protecting the tail from shear forces during epididymal transport and ejaculation. Defects in the outer dense fibers lead to abnormal sperm morphology and infertility. The human outer dense fibers contains at least 10 major proteins and this gene encodes the main protein. [provided by RefSeq, Jul 2008]

ODF1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ODF1	NM_024410.4 linkuse as main transcript	c.677C>T	p.Pro226Leu	missense_variant	2/2	ENST00000285402.4	NP_077721.2	Q14990

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ODF1	ENST00000285402.4 linkuse as main transcript	c.677C>T	p.Pro226Leu	missense_variant	2/2	1	NM_024410.4	ENSP00000285402.3		Q14990
ODF1	ENST00000518835.1 linkuse as main transcript	c.56C>T	p.Pro19Leu	missense_variant	2/2	3		ENSP00000430023.1		E5RH17

Frequencies

GnomAD3 genomes

AF:

0.000142

AC:

AN:

84690

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000133

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000117

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000205

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000410

AC:

AN:

243608

Hom.:

AF XY:

0.0000682

AC XY:

AN XY:

132052

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:

0.0000900

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000199

AC:

153

AN:

770134

Hom.:

Cov.:

AF XY:

0.000214

AC XY:

AN XY:

382334

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:

0.0000265

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000240

Gnomad4 OTH exome

AF:

0.000192

GnomAD4 genome

AF:

0.000142

AC:

AN:

84690

Hom.:

Cov.:

AF XY:

0.000145

AC XY:

AN XY:

41478

show subpopulations

Gnomad4 AFR

AF:

0.000133

Gnomad4 AMR

AF:

0.000117

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000205

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000175

Hom.:

Bravo

AF:

0.0000831

ESP6500AA

AF:

0.000459

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000573

AC:

EpiCase

AF:

0.000329

EpiControl

AF:

0.000119

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 01, 2021

The c.677C>T (p.P226L) alteration is located in exon 2 (coding exon 2) of the ODF1 gene. This alteration results from a C to T substitution at nucleotide position 677, causing the proline (P) at amino acid position 226 to be replaced by a leucine (L). 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

0.25

BayesDel_addAF

Benign

-0.082

BayesDel_noAF

Uncertain

-0.050

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.058

T;.

Eigen

Uncertain

0.28

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.81

T;T

M_CAP

Uncertain

0.095

MetaRNN

Uncertain

0.73

D;D

MetaSVM

Uncertain

0.49

MutationAssessor

Uncertain

2.1

M;.

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-4.2

D;D

REVEL

Uncertain

0.37

Sift

Pathogenic

0.0

D;D

Sift4G

Uncertain

0.014

D;D

Polyphen

0.94

P;.

Vest4

0.74

MVP

0.89

MPC

0.67

ClinPred

0.71

GERP RS

5.5

Varity_R

0.42

gMVP

0.31

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