1-54806136-C-T

Position:

• chr1-54806136-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001110533.2(LEXM):​c.20C>T​(p.Ala7Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000719 in 1,391,262 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: not found (cov: 31)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: LEXM NM_001110533.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.201

Genes affected

LEXM (HGNC:):

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]

ACMG classification

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=0.054244548).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LEXM	NM_001110533.2	c.20C>T	p.Ala7Val	missense_variant	1/10	ENST00000371273.4	NP_001104003.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CIMAP2	ENST00000371273.4	c.20C>T	p.Ala7Val	missense_variant	1/10	1	NM_001110533.2	ENSP00000360320	A2
CIMAP2	ENST00000358193.7	c.20C>T	p.Ala7Val	missense_variant	1/11	1		ENSP00000350924	P4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.19e-7 AC: 1 AN: 1391262 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 686990

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.25e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 21, 2022

The c.20C>T (p.A7V) alteration is located in exon 1 (coding exon 1) of the LEXM gene. This alteration results from a C to T substitution at nucleotide position 20, causing the alanine (A) at amino acid position 7 to be replaced by a valine (V). 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	0.13
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	1.9
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0014	.;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.031	N
LIST_S2	Benign	0.49	T;T
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.054	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N
PROVEAN	Benign	-0.64	N;N
REVEL	Benign	0.055
Sift	Benign	0.041	D;D
Sift4G	Benign	0.17	T;T
Polyphen		0.0080	B;B
Vest4		0.081
MutPred		0.18		Loss of disorder (P = 0.0749);Loss of disorder (P = 0.0749);
MVP		0.014
MPC		0.14
ClinPred		0.12	T
GERP RS		0.25
Varity_R		0.018
gMVP		0.072

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-55271809;