11-198582-C-G

Position:

chr11-198582-C-G

Variant summary

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

The NM_053280.5(CIMAP1A):c.531C>G(p.His177Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000411 in 1,607,126 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 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000043 ( 0 hom. )

Consequence

CIMAP1A
NM_053280.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.457

Variant links:

Genes affected

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:

ODF3 (HGNC:):

ODF3 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=0.025744021).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CIMAP1A	NM_053280.5 linkuse as main transcript	c.531C>G	p.His177Gln	missense_variant	5/7	ENST00000325113.9	NP_444510.2	Q96PU9-1
CIMAP1A	NM_001286136.2 linkuse as main transcript	c.531C>G	p.His177Gln	missense_variant	5/6		NP_001273065.1	Q96PU9-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ODF3	ENST00000325113.9 linkuse as main transcript	c.531C>G	p.His177Gln	missense_variant	5/7	1	NM_053280.5	ENSP00000325868.5	Q96PU9-1
ODF3	ENST00000525282.1 linkuse as main transcript	c.531C>G	p.His177Gln	missense_variant	5/6	1		ENSP00000436588.1	Q96PU9-3
BET1L	ENST00000410108.5 linkuse as main transcript	c.168+7029G>C		intron_variant		3		ENSP00000386558.1	B8ZZS0
ODF3	ENST00000531679.1 linkuse as main transcript	n.1374C>G		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152258

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

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:

0.0000611

AC:

AN:

245558

Hom.:

AF XY:

0.0000377

AC XY:

AN XY:

132710

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00126

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000271

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000433

AC:

AN:

1454868

Hom.:

Cov.:

AF XY:

0.0000484

AC XY:

AN XY:

723050

show subpopulations

Gnomad4 AFR exome

AF:

0.000210

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00156

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000451

Gnomad4 OTH exome

AF:

0.000150

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152258

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000228

Hom.:

Bravo

AF:

0.0000340

ExAC

AF:

0.0000577

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 25, 2022

The c.531C>G (p.H177Q) alteration is located in exon 5 (coding exon 4) of the ODF3 gene. This alteration results from a C to G substitution at nucleotide position 531, causing the histidine (H) at amino acid position 177 to be replaced by a glutamine (Q). 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

0.14

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.0029

T;.;.

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.25

FATHMM_MKL

Benign

0.38

LIST_S2

Benign

0.61

T;T;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.026

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.20

N;N;.

PrimateAI

Uncertain

0.49

PROVEAN

Benign

1.2

N;N;.

REVEL

Benign

0.056

Sift

Benign

0.72

T;T;.

Sift4G

Benign

0.76

T;T;T

Polyphen

0.65

P;.;.

Vest4

0.20

MutPred

0.25

Loss of catalytic residue at H177 (P = 0.0845);Loss of catalytic residue at H177 (P = 0.0845);.;

MVP

0.24

MPC

0.26

ClinPred

0.084

GERP RS

3.8

Varity_R

0.14

gMVP

0.34

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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