1-77916039-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_144573.4(NEXN):​c.-52-16T>C 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 0.000736 in 955,414 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00049 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00078 ( 1 hom. )

Consequence

NEXN
NM_144573.4 splice_polypyrimidine_tract, intron

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.509
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
BP6
Variant 1-77916039-T-C is Benign according to our data. Variant chr1-77916039-T-C is described in ClinVar as [Benign]. Clinvar id is 201911.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000487 (74/152046) while in subpopulation AMR AF= 0.000786 (12/15276). AF 95% confidence interval is 0.000612. There are 0 homozygotes in gnomad4. There are 28 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High AC in GnomAd4 at 74 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NEXNNM_144573.4 linkuse as main transcriptc.-52-16T>C splice_polypyrimidine_tract_variant, intron_variant ENST00000334785.12 NP_653174.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NEXNENST00000334785.12 linkuse as main transcriptc.-52-16T>C splice_polypyrimidine_tract_variant, intron_variant 1 NM_144573.4 ENSP00000333938 P3Q0ZGT2-1
NEXNENST00000401035.7 linkuse as main transcriptc.-52-16T>C splice_polypyrimidine_tract_variant, intron_variant 1 ENSP00000383814
NEXNENST00000330010.12 linkuse as main transcriptc.-52-16T>C splice_polypyrimidine_tract_variant, intron_variant 2 ENSP00000327363 A1Q0ZGT2-4
NEXNENST00000440324.5 linkuse as main transcriptc.-52-16T>C splice_polypyrimidine_tract_variant, intron_variant 5 ENSP00000411902

Frequencies

GnomAD3 genomes
AF:
0.000487
AC:
74
AN:
151932
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000121
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000787
Gnomad ASJ
AF:
0.000288
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000780
Gnomad OTH
AF:
0.00143
GnomAD4 exome
AF:
0.000783
AC:
629
AN:
803368
Hom.:
1
Cov.:
10
AF XY:
0.000808
AC XY:
328
AN XY:
406110
show subpopulations
Gnomad4 AFR exome
AF:
0.0000602
Gnomad4 AMR exome
AF:
0.00125
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000106
Gnomad4 FIN exome
AF:
0.0000283
Gnomad4 NFE exome
AF:
0.000912
Gnomad4 OTH exome
AF:
0.000770
GnomAD4 genome
AF:
0.000487
AC:
74
AN:
152046
Hom.:
0
Cov.:
33
AF XY:
0.000377
AC XY:
28
AN XY:
74358
show subpopulations
Gnomad4 AFR
AF:
0.000120
Gnomad4 AMR
AF:
0.000786
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000780
Gnomad4 OTH
AF:
0.00142
Alfa
AF:
0.000624
Hom.:
0
Bravo
AF:
0.000774

ClinVar

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

Submissions by phenotype

not specified Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxSep 17, 2014This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.78
CADD
Benign
2.4
DANN
Benign
0.75

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs557864364; hg19: chr1-78381724; API