Variant 1-54811901-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001110533.2(CIMAP2):c.588G>A(p.Met196Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,844 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 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: 0.0000027 ( 0 hom. )

Consequence

CIMAP2
NM_001110533.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.70

Variant links:

Genes affected

CIMAP2 (HGNC:26854): (ciliary microtubule associated protein 2) Predicted to enable mitochondrial ribosome binding activity. Predicted to act upstream of or within positive regulation of cell population proliferation and positive regulation of oxidative phosphorylation. Predicted to be located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

CIMAP2 links:

CIMAP2 (HGNC:):

CIMAP2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.106858134).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CIMAP2	NM_001110533.2 linkuse as main transcript	c.588G>A	p.Met196Ile	missense_variant	5/10	ENST00000371273.4	NP_001104003.1	Q3ZCV2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LEXM	ENST00000371273.4 linkuse as main transcript	c.588G>A	p.Met196Ile	missense_variant	5/10	1	NM_001110533.2	ENSP00000360320.3		Q3ZCV2-1
LEXM	ENST00000358193.7 linkuse as main transcript	c.588G>A	p.Met196Ile	missense_variant	5/11	1		ENSP00000350924.3		Q3ZCV2-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251430

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135908

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:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461844

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727218

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:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

May 06, 2024

The c.588G>A (p.M196I) alteration is located in exon 5 (coding exon 5) of the LEXM gene. This alteration results from a G to A substitution at nucleotide position 588, causing the methionine (M) at amino acid position 196 to be replaced by an isoleucine (I). 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

Uncertain

0.35

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.015

.;T

Eigen

Benign

0.0077

Eigen_PC

Benign

0.14

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.73

T;T

M_CAP

Benign

0.0060

MetaRNN

Benign

0.11

T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

0.87

N;N

PROVEAN

Benign

-1.8

N;N

REVEL

Benign

0.017

Sift

Benign

0.22

T;T

Sift4G

Benign

0.20

T;T

Polyphen

0.21

B;B

Vest4

0.15

MutPred

0.27

Loss of disorder (P = 0.0448);Loss of disorder (P = 0.0448);

MVP

0.13

MPC

0.15

ClinPred

0.59

GERP RS

4.7

Varity_R

0.37

gMVP

0.44

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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