Variant 1-54812118-A-C 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(LEXM):c.691A>C(p.Thr231Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,614,112 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

LEXM
NM_001110533.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.36

Variant links:

Genes affected

LEXM (HGNC:):

LEXM links:

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:

Genome browser will be placed here

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=0.12939274).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LEXM	NM_001110533.2 linkuse as main transcript	c.691A>C	p.Thr231Pro	missense_variant	6/10	ENST00000371273.4	NP_001104003.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CIMAP2	ENST00000371273.4 linkuse as main transcript	c.691A>C	p.Thr231Pro	missense_variant	6/10	1	NM_001110533.2	ENSP00000360320	A2	Q3ZCV2-1
CIMAP2	ENST00000358193.7 linkuse as main transcript	c.691A>C	p.Thr231Pro	missense_variant	6/11	1		ENSP00000350924	P4	Q3ZCV2-2

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152110

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000199

AC:

AN:

251482

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135916

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000130

AC:

AN:

1461884

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.000128

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152228

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000247

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

Oct 05, 2023

The c.691A>C (p.T231P) alteration is located in exon 6 (coding exon 6) of the LEXM gene. This alteration results from a A to C substitution at nucleotide position 691, causing the threonine (T) at amino acid position 231 to be replaced by a proline (P). 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

-0.30

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.015

.;T

Eigen

Benign

-0.091

Eigen_PC

Benign

-0.20

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.56

T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.13

T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

N;N

PROVEAN

Uncertain

-2.9

D;D

REVEL

Benign

0.14

Sift

Benign

0.058

T;T

Sift4G

Benign

0.12

T;T

Polyphen

0.90

P;P

Vest4

0.33

MutPred

0.17

Loss of glycosylation at T231 (P = 0.018);Loss of glycosylation at T231 (P = 0.018);

MVP

0.11

MPC

0.59

ClinPred

0.51

GERP RS

3.9

Varity_R

0.10

gMVP

0.55

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

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