chr11-200020-T-C

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_053280.5(CIMAP1A):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. 15/22 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

CIMAP1A
NM_053280.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.30

Publications

4 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.1375629).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIMAP1A	NM_053280.5 link	c.752T>C	p.Val251Ala	missense_variant	Exon 7 of 7	ENST00000325113.9	NP_444510.2	Q96PU9-1
CIMAP1A	NM_001286136.2 link	c.611T>C	p.Val204Ala	missense_variant	Exon 6 of 6		NP_001273065.1	Q96PU9-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CIMAP1A	ENST00000325113.9 link	c.752T>C	p.Val251Ala	missense_variant	Exon 7 of 7	1	NM_053280.5	ENSP00000325868.5	Q96PU9-1
CIMAP1A	ENST00000525282.1 link	c.611T>C	p.Val204Ala	missense_variant	Exon 6 of 6	1		ENSP00000436588.1	Q96PU9-3
CIMAP1A	ENST00000531679.1 link	n.2812T>C		non_coding_transcript_exon_variant	Exon 3 of 3	2
BET1L	ENST00000410108.5 link	c.168+5591A>G		intron_variant	Intron 3 of 5	3		ENSP00000386558.1	B8ZZS0

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

GnomAD2 exomes

AF:

0.000299

AC:

AN:

250562

AF XY:

0.000325

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 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

African (AFR)

AF:

0.0000597

AC:

AN:

33480

American (AMR)

AF:

0.0000224

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.000131

AC:

AN:

53258

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000920

AC:

1023

AN:

1111974

Other (OTH)

AF:

0.000679

AC:

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

112

169

225

281

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

120

160

200

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000388

AC:

AN:

152188

Hom.:

Cov.:

AF XY:

0.000282

AC XY:

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.000121

AC:

AN:

41458

American (AMR)

AF:

0.00

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.000188

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000735

AC:

AN:

68028

Other (OTH)

AF:

0.000955

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000668

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

Aug 10, 2021

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

(source)

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;.;.

PhyloP100

3.3

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

Mutation Taster

=81/19

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over