chr1-77916140-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_144573.4(NEXN):​c.27+7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Consequence

NEXN
NM_144573.4 splice_region, intron

Scores

2
Splicing: ADA: 0.00003098
2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.146
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 Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.7).
BP6
Variant 1-77916140-C-T is Benign according to our data. Variant chr1-77916140-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1648949.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NEXNNM_144573.4 linkuse as main transcriptc.27+7C>T splice_region_variant, intron_variant ENST00000334785.12

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NEXNENST00000334785.12 linkuse as main transcriptc.27+7C>T splice_region_variant, intron_variant 1 NM_144573.4 P3Q0ZGT2-1
NEXNENST00000401035.7 linkuse as main transcriptc.27+7C>T splice_region_variant, intron_variant 1
NEXNENST00000330010.12 linkuse as main transcriptc.27+7C>T splice_region_variant, intron_variant 2 A1Q0ZGT2-4
NEXNENST00000440324.5 linkuse as main transcriptc.27+7C>T splice_region_variant, intron_variant 5

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
27
GnomAD4 genome
Cov.:
33

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 testingLabcorp Genetics (formerly Invitae), LabcorpMay 03, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.70
CADD
Benign
4.6
DANN
Benign
0.62

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.000031
dbscSNV1_RF
Benign
0.014
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-78381825; API