rs201763096

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_144573.4(NEXN):c.995A>C(p.Glu332Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00335 in 1,613,478 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E332K) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0029 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0034 ( 28 hom. )

Consequence

NEXN
NM_144573.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts U:1B:19

Conservation

PhyloP100: 4.10

Publications

15 publications found

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]

NEXN Gene-Disease associations (from GenCC):

dilated cardiomyopathy
Inheritance: AD Classification: STRONG Submitted by: ClinGen
familial isolated dilated cardiomyopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
dilated cardiomyopathy 1CC
Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
hypertrophic cardiomyopathy
Inheritance: AD Classification: LIMITED Submitted by: ClinGen
hypertrophic cardiomyopathy 20
Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

NEXN links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00764665).

BP6

Variant 1-77929446-A-C is Benign according to our data. Variant chr1-77929446-A-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 47915.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00289 (440/152322) while in subpopulation SAS AF = 0.0128 (62/4828). AF 95% confidence interval is 0.0103. There are 2 homozygotes in GnomAd4. There are 240 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 440 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144573.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEXN	NM_144573.4	MANE Select	c.995A>C	p.Glu332Ala	missense	Exon 9 of 13	NP_653174.3	Q0ZGT2-1
	NEXN	NM_001172309.2		c.803A>C	p.Glu268Ala	missense	Exon 8 of 12	NP_001165780.1	Q0ZGT2-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NEXN	ENST00000334785.12	TSL:1 MANE Select	c.995A>C	p.Glu332Ala	missense	Exon 9 of 13	ENSP00000333938.7	Q0ZGT2-1
NEXN	ENST00000342754.5	TSL:1	c.692A>C	p.Glu231Ala	missense	Exon 5 of 10	ENSP00000343928.5	H7BXY5
NEXN	ENST00000401035.7	TSL:1	c.803A>C	p.Glu268Ala	missense	Exon 8 of 9	ENSP00000383814.3	E7ETM8

Frequencies

GnomAD3 genomes

AF:

0.00288

AC:

438

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000868

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00268

Gnomad ASJ

AF:

0.00289

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0124

Gnomad FIN

AF:

0.00688

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00306

Gnomad OTH

AF:

0.00287

GnomAD2 exomes

AF:

0.00427

AC:

1052

AN:

246598

AF XY:

0.00497

show subpopulations

Gnomad AFR exome

AF:

0.000970

Gnomad AMR exome

AF:

0.00162

Gnomad ASJ exome

AF:

0.00299

Gnomad EAS exome

AF:

0.000223

Gnomad FIN exome

AF:

0.00761

Gnomad NFE exome

AF:

0.00313

Gnomad OTH exome

AF:

0.00398

GnomAD4 exome

AF:

0.00340

AC:

4964

AN:

1461156

Hom.:

Cov.:

AF XY:

0.00371

AC XY:

2695

AN XY:

726912

show subpopulations

African (AFR)

AF:

0.000777

AC:

AN:

33456

American (AMR)

AF:

0.00163

AC:

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.00276

AC:

AN:

26122

East Asian (EAS)

AF:

0.000151

AC:

AN:

39634

South Asian (SAS)

AF:

0.0129

AC:

1114

AN:

86226

European-Finnish (FIN)

AF:

0.00560

AC:

299

AN:

53416

Middle Eastern (MID)

AF:

0.00833

AC:

AN:

5644

European-Non Finnish (NFE)

AF:

0.00280

AC:

3108

AN:

1111596

Other (OTH)

AF:

0.00363

AC:

219

AN:

60350

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

254

509

763

1018

1272

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

116

232

348

464

580

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00289

AC:

440

AN:

152322

Hom.:

Cov.:

AF XY:

0.00322

AC XY:

240

AN XY:

74494

show subpopulations

African (AFR)

AF:

0.000866

AC:

AN:

41574

American (AMR)

AF:

0.00268

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00289

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.0128

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00688

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00306

AC:

208

AN:

68024

Other (OTH)

AF:

0.00284

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

107

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00308

Hom.:

Bravo

AF:

0.00212

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.00285

AC:

ESP6500AA

AF:

0.00108

AC:

ESP6500EA

AF:

0.00244

AC:

ExAC

AF:

0.00397

AC:

480

Asia WGS

AF:

0.00664

AC:

AN:

3478

EpiCase

AF:

0.00382

EpiControl

AF:

0.00302

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (9)

not provided (5)

Dilated cardiomyopathy 1CC;C3151267:Hypertrophic cardiomyopathy 20 (2)

Cardiomyopathy (1)

Cardiovascular phenotype (1)

Hypertrophic cardiomyopathy (1)

Premature ventricular contraction (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.28

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.25

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.82

MetaRNN

Benign

0.0076

MetaSVM

Benign

-0.44

MutationAssessor

Pathogenic

3.1

PhyloP100

4.1

PrimateAI

Benign

0.47

PROVEAN

Uncertain

-3.0

REVEL

Benign

0.16

Sift

Uncertain

0.027

Sift4G

Uncertain

0.010

Polyphen

0.0

Vest4

0.22

MVP

0.86

MPC

0.049

ClinPred

0.068

GERP RS

5.0

Varity_R

0.14

gMVP

0.12

Mutation Taster

=95/5

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over