Variant 11-197395-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000325113.9(CIMAP1A):c.91C>G(p.Leu31Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00004 in 1,449,460 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: 0.000040 ( 0 hom. )

Consequence

CIMAP1A
ENST00000325113.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.427

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 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=0.06463602).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ODF3	NM_053280.5 linkuse as main transcript	c.91C>G	p.Leu31Val	missense_variant	2/7	ENST00000325113.9	NP_444510.2
ODF3	NM_001286136.2 linkuse as main transcript	c.91C>G	p.Leu31Val	missense_variant	2/6		NP_001273065.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CIMAP1A	ENST00000325113.9 linkuse as main transcript	c.91C>G	p.Leu31Val	missense_variant	2/7	1	NM_053280.5	ENSP00000325868	P1	Q96PU9-1
CIMAP1A	ENST00000525282.1 linkuse as main transcript	c.91C>G	p.Leu31Val	missense_variant	2/6	1		ENSP00000436588		Q96PU9-3
BET1L	ENST00000410108.5 linkuse as main transcript	c.168+8216G>C		intron_variant		3		ENSP00000386558
CIMAP1A	ENST00000531679.1 linkuse as main transcript	n.601C>G		non_coding_transcript_exon_variant	1/3	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000883

AC:

AN:

226484

Hom.:

AF XY:

0.00000814

AC XY:

AN XY:

122852

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:

0.0000199

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000400

AC:

AN:

1449460

Hom.:

Cov.:

AF XY:

0.0000417

AC XY:

AN XY:

720134

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:

0.0000488

Gnomad4 OTH exome

AF:

0.0000668

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

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

Apr 22, 2022

The c.91C>G (p.L31V) alteration is located in exon 2 (coding exon 1) of the ODF3 gene. This alteration results from a C to G substitution at nucleotide position 91, causing the leucine (L) at amino acid position 31 to be replaced by a valine (V). 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

0.093

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.0075

T;.;.

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.056

LIST_S2

Benign

0.58

T;T;T

M_CAP

Benign

0.0067

MetaRNN

Benign

0.065

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.63

N;N;.

MutationTaster

Benign

1.0

D;N;N;N

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.21

N;N;N

REVEL

Benign

0.052

Sift

Benign

0.49

T;T;T

Sift4G

Benign

0.54

T;T;T

Polyphen

0.31

B;.;P

Vest4

0.11

MutPred

0.24

Loss of catalytic residue at L31 (P = 0.1325);Loss of catalytic residue at L31 (P = 0.1325);Loss of catalytic residue at L31 (P = 0.1325);

MVP

0.27

MPC

0.25

ClinPred

0.052

GERP RS

0.76

Varity_R

0.10

gMVP

0.38

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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