dbSNP rs139806480: CIMAP1A:p.Val251Asp (chr11-200020-T-A) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_053280.5(CIMAP1A):c.752T>A(p.Val251Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,682 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V251A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CIMAP1A
NM_053280.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.30

Publications

0 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: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.768

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIMAP1A	NM_053280.5 link	c.752T>A	p.Val251Asp	missense_variant	Exon 7 of 7	ENST00000325113.9	NP_444510.2	Q96PU9-1
CIMAP1A	NM_001286136.2 link	c.611T>A	p.Val204Asp	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>A	p.Val251Asp	missense_variant	Exon 7 of 7	1	NM_053280.5	ENSP00000325868.5	Q96PU9-1
CIMAP1A	ENST00000525282.1 link	c.611T>A	p.Val204Asp	missense_variant	Exon 6 of 6	1		ENSP00000436588.1	Q96PU9-3
CIMAP1A	ENST00000531679.1 link	n.2812T>A		non_coding_transcript_exon_variant	Exon 3 of 3	2
BET1L	ENST00000410108.5 link	c.168+5591A>T		intron_variant	Intron 3 of 5	3		ENSP00000386558.1	B8ZZS0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461682

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727122

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53258

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111974

Other (OTH)

AF:

0.00

AC:

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.31

BayesDel_addAF

Pathogenic

0.19

BayesDel_noAF

Uncertain

0.040

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.15

T;.;.

Eigen

Uncertain

0.30

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.80

T;T;T

M_CAP

Benign

0.078

MetaRNN

Pathogenic

0.77

D;D;D

MetaSVM

Benign

-0.79

MutationAssessor

Uncertain

2.3

M;.;.

PhyloP100

3.3

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-3.8

D;D;.

REVEL

Uncertain

0.34

Sift

Uncertain

0.0020

D;D;.

Sift4G

Uncertain

0.0020

D;D;D

Polyphen

0.97

D;.;.

Vest4

0.87

MutPred

0.49

Gain of disorder (P = 0.023);.;.;

MVP

0.80

MPC

0.72

ClinPred

0.98

GERP RS

5.0

Varity_R

0.66

gMVP

0.82

Mutation Taster

=79/21

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over