chr1-77917554-C-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_144573.4(NEXN):​c.28-12C>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000416 in 1,442,502 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: 0.0000042 ( 0 hom. )

Consequence

NEXN
NM_144573.4 splice_polypyrimidine_tract, intron

Scores

2
Splicing: ADA: 0.9105
2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.48
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 Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.23).
BP6
Variant 1-77917554-C-A is Benign according to our data. Variant chr1-77917554-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 2040650.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NEXNNM_144573.4 linkuse as main transcriptc.28-12C>A splice_polypyrimidine_tract_variant, intron_variant ENST00000334785.12

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NEXNENST00000334785.12 linkuse as main transcriptc.28-12C>A splice_polypyrimidine_tract_variant, intron_variant 1 NM_144573.4 P3Q0ZGT2-1
NEXNENST00000401035.7 linkuse as main transcriptc.28-406C>A intron_variant 1
NEXNENST00000330010.12 linkuse as main transcriptc.28-406C>A intron_variant 2 A1Q0ZGT2-4
NEXNENST00000440324.5 linkuse as main transcriptc.28-12C>A splice_polypyrimidine_tract_variant, intron_variant 5

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000406
AC:
1
AN:
246034
Hom.:
0
AF XY:
0.00000748
AC XY:
1
AN XY:
133718
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:
0.00000897
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000416
AC:
6
AN:
1442502
Hom.:
0
Cov.:
29
AF XY:
0.00000557
AC XY:
4
AN XY:
718462
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:
0.00000547
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000378

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Dilated cardiomyopathy 1CC;C3151267:Hypertrophic cardiomyopathy 20 Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeMar 31, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.23
CADD
Benign
21
DANN
Benign
0.74

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.91
dbscSNV1_RF
Benign
0.64
SpliceAI score (max)
0.060
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: rs1169196192; hg19: chr1-78383239; API