1-77917570-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_144573.4(NEXN):​c.32T>C​(p.Leu11Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

NEXN
NM_144573.4 missense

Scores

10
6
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.55
Variant links:
Genes affected
NEXN (HGNC:29557): (nexilin F-actin binding protein) This gene encodes a filamentous actin-binding protein that may function in cell adhesion and migration. Mutations in this gene have been associated with dilated cardiomyopathy, also known as CMD1CC. Alternatively spliced transcript variants have been described.[provided by RefSeq, Feb 2010]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NEXNNM_144573.4 linkuse as main transcriptc.32T>C p.Leu11Pro missense_variant 3/13 ENST00000334785.12 NP_653174.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NEXNENST00000334785.12 linkuse as main transcriptc.32T>C p.Leu11Pro missense_variant 3/131 NM_144573.4 ENSP00000333938 P3Q0ZGT2-1
NEXNENST00000401035.7 linkuse as main transcriptc.28-390T>C intron_variant 1 ENSP00000383814
NEXNENST00000440324.5 linkuse as main transcriptc.32T>C p.Leu11Pro missense_variant 3/105 ENSP00000411902
NEXNENST00000330010.12 linkuse as main transcriptc.28-390T>C intron_variant 2 ENSP00000327363 A1Q0ZGT2-4

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsFeb 11, 2022The p.L11P variant (also known as c.32T>C), located in coding exon 2 of the NEXN gene, results from a T to C substitution at nucleotide position 32. The leucine at codon 11 is replaced by proline, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.91
BayesDel_addAF
Pathogenic
0.38
D
BayesDel_noAF
Pathogenic
0.31
CADD
Pathogenic
27
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.047
T;T
Eigen
Pathogenic
0.74
Eigen_PC
Pathogenic
0.73
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.88
D;D
M_CAP
Uncertain
0.20
D
MetaRNN
Uncertain
0.70
D;D
MetaSVM
Uncertain
0.13
D
MutationAssessor
Uncertain
2.6
M;.
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Pathogenic
0.82
D
PROVEAN
Benign
-1.9
N;N
REVEL
Pathogenic
0.67
Sift
Pathogenic
0.0
D;D
Sift4G
Uncertain
0.014
D;T
Polyphen
1.0
D;.
Vest4
0.90
MutPred
0.46
Gain of sheet (P = 0.0085);Gain of sheet (P = 0.0085);
MVP
0.93
MPC
0.39
ClinPred
0.99
D
GERP RS
5.4
Varity_R
0.72
gMVP
0.71

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: chr1-78383255; API