Genetic Variant NEXN:c.28-9C>T (chr1-77917557-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_ModerateBP6_Very_StrongBS2

The NM_144573.4(NEXN):c.28-9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000311 in 1,446,130 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 Likely benign (★★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000031 ( 0 hom. )

Consequence

NEXN
NM_144573.4 intron

Scores

Splicing: ADA: 0.3292

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.05

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 Gene-Disease associations (from GenCC):

dilated cardiomyopathy
Inheritance: AD Classification: MODERATE 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: PanelApp Australia, 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.25).

BP6

Variant 1-77917557-C-T is Benign according to our data. Variant chr1-77917557-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1205626.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAdExome4 at 45 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEXN	NM_144573.4 link	c.28-9C>T		intron_variant	Intron 2 of 12	ENST00000334785.12	NP_653174.3	Q0ZGT2-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
NEXN	ENST00000334785.12 link	c.28-9C>T	intron_variant	Intron 2 of 12	1	NM_144573.4	ENSP00000333938.7	Q0ZGT2-1
NEXN	ENST00000401035.7 link	c.28-403C>T	intron_variant	Intron 2 of 8	1		ENSP00000383814.3	E7ETM8
NEXN	ENST00000330010.12 link	c.28-403C>T	intron_variant	Intron 2 of 11	2		ENSP00000327363.8	Q0ZGT2-4
NEXN	ENST00000440324.5 link	c.28-9C>T	intron_variant	Intron 2 of 9	5		ENSP00000411902.1	E7EUA0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000809

AC:

AN:

247180

AF XY:

0.00000745

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000178

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000311

AC:

AN:

1446130

Hom.:

Cov.:

AF XY:

0.0000306

AC XY:

AN XY:

720070

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33062

American (AMR)

AF:

0.00

AC:

AN:

44456

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25940

East Asian (EAS)

AF:

0.00

AC:

AN:

39252

South Asian (SAS)

AF:

0.00

AC:

AN:

85132

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53320

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5722

European-Non Finnish (NFE)

AF:

0.0000400

AC:

AN:

1099482

Other (OTH)

AF:

0.0000167

AC:

AN:

59764

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Nov 26, 2019

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dilated cardiomyopathy 1CC;C3151267:Hypertrophic cardiomyopathy 20

Benign:1

May 25, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.25

CADD

Benign

(source)

DANN

Benign

0.68

PhyloP100

2.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.33

dbscSNV1_RF

Benign

0.45

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

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1-77917557-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over