1-77917581-T-C

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_144573.4(NEXN):ā€‹c.43T>Cā€‹(p.Ser15Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000548 in 1,460,798 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000055 ( 0 hom. )

Consequence

NEXN
NM_144573.4 missense

Scores

9
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.25
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 -5 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.27834833).
BS2
High AC in GnomAdExome4 at 8 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NEXNNM_144573.4 linkuse as main transcriptc.43T>C p.Ser15Pro 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.43T>C p.Ser15Pro missense_variant 3/131 NM_144573.4 ENSP00000333938 P3Q0ZGT2-1
NEXNENST00000401035.7 linkuse as main transcriptc.28-379T>C intron_variant 1 ENSP00000383814
NEXNENST00000440324.5 linkuse as main transcriptc.43T>C p.Ser15Pro missense_variant 3/105 ENSP00000411902
NEXNENST00000330010.12 linkuse as main transcriptc.28-379T>C intron_variant 2 ENSP00000327363 A1Q0ZGT2-4

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000548
AC:
8
AN:
1460798
Hom.:
0
Cov.:
31
AF XY:
0.00000550
AC XY:
4
AN XY:
726708
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:
0.00000720
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

Cardiomyopathy Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingCHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern OntarioMar 16, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.42
BayesDel_addAF
Uncertain
0.10
D
BayesDel_noAF
Benign
-0.090
CADD
Uncertain
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.013
T;T
Eigen
Uncertain
0.30
Eigen_PC
Uncertain
0.38
FATHMM_MKL
Uncertain
0.86
D
LIST_S2
Benign
0.85
D;T
M_CAP
Benign
0.038
D
MetaRNN
Benign
0.28
T;T
MetaSVM
Benign
-0.64
T
MutationAssessor
Benign
1.9
L;.
MutationTaster
Benign
1.0
D;N;N;N
PrimateAI
Uncertain
0.58
T
PROVEAN
Benign
-1.5
N;N
REVEL
Benign
0.19
Sift
Uncertain
0.0090
D;D
Sift4G
Uncertain
0.044
D;T
Polyphen
0.67
P;.
Vest4
0.50
MutPred
0.22
Gain of loop (P = 0.0312);Gain of loop (P = 0.0312);
MVP
0.75
MPC
0.17
ClinPred
0.85
D
GERP RS
5.5
Varity_R
0.44
gMVP
0.22

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: chr1-78383266; API