1-77917567-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_144573.4(NEXN):ā€‹c.29T>Gā€‹(p.Ile10Ser) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000000687 in 1,456,168 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 6.9e-7 ( 0 hom. )

Consequence

NEXN
NM_144573.4 missense, splice_region

Scores

2
9
8
Splicing: ADA: 0.4403
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.88
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.33517525).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NEXNNM_144573.4 linkuse as main transcriptc.29T>G p.Ile10Ser missense_variant, splice_region_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.29T>G p.Ile10Ser missense_variant, splice_region_variant 3/131 NM_144573.4 ENSP00000333938 P3Q0ZGT2-1
NEXNENST00000401035.7 linkuse as main transcriptc.28-393T>G intron_variant 1 ENSP00000383814
NEXNENST00000440324.5 linkuse as main transcriptc.29T>G p.Ile10Ser missense_variant, splice_region_variant 3/105 ENSP00000411902
NEXNENST00000330010.12 linkuse as main transcriptc.28-393T>G intron_variant 2 ENSP00000327363 A1Q0ZGT2-4

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.87e-7
AC:
1
AN:
1456168
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
724650
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
33

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 GeneticsMay 11, 2023The p.I10S variant (also known as c.29T>G), located in coding exon 2 of the NEXN gene, results from a T to G substitution at nucleotide position 29. The isoleucine at codon 10 is replaced by serine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. 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
0.79
BayesDel_addAF
Pathogenic
0.17
D
BayesDel_noAF
Uncertain
0.0
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Benign
0.025
T;T
Eigen
Uncertain
0.39
Eigen_PC
Uncertain
0.46
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.88
D;D
M_CAP
Benign
0.051
D
MetaRNN
Benign
0.34
T;T
MetaSVM
Benign
-0.76
T
MutationAssessor
Uncertain
2.6
M;.
MutationTaster
Benign
0.81
D;D;D;D
PrimateAI
Uncertain
0.75
T
PROVEAN
Benign
-0.12
N;N
REVEL
Benign
0.21
Sift
Uncertain
0.028
D;D
Sift4G
Benign
0.20
T;T
Polyphen
0.87
P;.
Vest4
0.67
MutPred
0.33
Loss of stability (P = 0.0263);Loss of stability (P = 0.0263);
MVP
0.78
MPC
0.19
ClinPred
0.90
D
GERP RS
5.3
Varity_R
0.20
gMVP
0.32

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.44
dbscSNV1_RF
Benign
0.34
SpliceAI score (max)
0.17
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: chr1-78383252; API