Genetic Variant NEXN:c.-197_-195dupGGC (chr1-77888598-A-ACGG) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The ENST00000421331.1(NEXN-AS1):n.740_742dupCCG variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000163 in 172,210 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00035 ( 1 hom. )

Consequence

NEXN-AS1
ENST00000421331.1 non_coding_transcript_exon

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:3

Conservation

PhyloP100: 0.937

Publications

0 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 links:

NEXN-AS1 (HGNC:31983): (NEXN antisense RNA 1)

NEXN-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEXN	NM_144573.4 link	c.-214_-213insCGG		upstream_gene_variant		ENST00000334785.12	NP_653174.3	Q0ZGT2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEXN	ENST00000334785.12 link	c.-214_-213insCGG		upstream_gene_variant		1	NM_144573.4	ENSP00000333938.7		Q0ZGT2-1

Frequencies

GnomAD3 genomes

AF:

0.000138

AC:

AN:

151882

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000328

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000346

AC:

AN:

20212

Hom.:

Cov.:

AF XY:

0.000213

AC XY:

AN XY:

14114

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

234

American (AMR)

AF:

0.00

AC:

AN:

258

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

224

East Asian (EAS)

AF:

0.00

AC:

AN:

508

South Asian (SAS)

AF:

0.000902

AC:

AN:

3326

European-Finnish (FIN)

AF:

0.00

AC:

AN:

922

Middle Eastern (MID)

AF:

0.00

AC:

AN:

134

European-Non Finnish (NFE)

AF:

0.000289

AC:

AN:

13848

Other (OTH)

AF:

0.00

AC:

AN:

758

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.655

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000138

AC:

AN:

151998

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.000121

AC:

AN:

41464

American (AMR)

AF:

0.000327

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5152

South Asian (SAS)

AF:

0.00

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10594

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000147

AC:

AN:

67916

Other (OTH)

AF:

0.00

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.000113

Asia WGS

AF:

0.000578

AC:

AN:

3476

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Dilated Cardiomyopathy, Dominant

Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Uncertain:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Hypertrophic cardiomyopathy

Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.94

Mutation Taster

=297/3

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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1-77888598-A-ACGG

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over