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rs146245480

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_144573.4(NEXN):c.835C>A(p.Arg279Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000013 in 1,613,744 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R279C) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

NEXN
NM_144573.4 missense

Scores

8
10

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.69
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 Likely_benign. Variant got -1 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.26797128).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NEXNNM_144573.4 linkuse as main transcriptc.835C>A p.Arg279Ser missense_variant 8/13 ENST00000334785.12

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NEXNENST00000334785.12 linkuse as main transcriptc.835C>A p.Arg279Ser missense_variant 8/131 NM_144573.4 P3Q0ZGT2-1

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
152066
Hom.:
0
Cov.:
32
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:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000161
AC:
4
AN:
248452
Hom.:
0
AF XY:
0.0000222
AC XY:
3
AN XY:
134980
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:
0.0000356
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000137
AC:
20
AN:
1461678
Hom.:
0
Cov.:
32
AF XY:
0.0000110
AC XY:
8
AN XY:
727138
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:
0.0000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000658
AC:
1
AN:
152066
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74278
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
ExAC
AF:
0.0000248
AC:
3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.38
BayesDel_addAF
Benign
0.00030
T
BayesDel_noAF
Benign
-0.13
Cadd
Uncertain
25
Dann
Uncertain
1.0
DEOGEN2
Benign
0.070
T;.;T;T
Eigen
Uncertain
0.40
Eigen_PC
Uncertain
0.43
FATHMM_MKL
Uncertain
0.88
D
LIST_S2
Uncertain
0.88
D;D;D;D
M_CAP
Benign
0.057
D
MetaRNN
Benign
0.27
T;T;T;T
MetaSVM
Benign
-0.40
T
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Benign
0.32
T
PROVEAN
Benign
-1.5
N;N;N;N
REVEL
Benign
0.15
Sift
Uncertain
0.0020
D;D;D;D
Sift4G
Uncertain
0.0050
D;D;D;D
Polyphen
0.98
.;.;D;.
Vest4
0.70, 0.61
MutPred
0.27
.;.;Gain of phosphorylation at R279 (P = 0.0037);.;
MVP
0.86
MPC
0.23
ClinPred
0.71
D
GERP RS
5.6
Varity_R
0.27
gMVP
0.14

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.

Other links and lift over

dbSNP: rs146245480; hg19: chr1-78392548; API