Variant 1-77917567-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_144573.4(NEXN):c.29T>G(p.Ile10Ser) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000000687 in 1,456,168 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

NEXN
NM_144573.4 missense, splice_region

Scores

Splicing: ADA: 0.4403

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.88

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.33517525).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEXN	NM_144573.4 linkuse as main transcript	c.29T>G	p.Ile10Ser	missense_variant, splice_region_variant	3/13	ENST00000334785.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEXN	ENST00000334785.12 linkuse as main transcript	c.29T>G	p.Ile10Ser	missense_variant, splice_region_variant	3/13	1	NM_144573.4	P3	Q0ZGT2-1
NEXN	ENST00000401035.7 linkuse as main transcript	c.28-393T>G		intron_variant		1
NEXN	ENST00000440324.5 linkuse as main transcript	c.29T>G	p.Ile10Ser	missense_variant, splice_region_variant	3/10	5
NEXN	ENST00000330010.12 linkuse as main transcript	c.28-393T>G		intron_variant		2		A1	Q0ZGT2-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1456168

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724650

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:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Cardiovascular phenotype

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 11, 2023

The p.I10S variant (also known as c.29T>G), located in coding exon 2 of the NEXN gene, results from a T to G substitution at nucleotide position 29. The isoleucine at codon 10 is replaced by serine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.79

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Uncertain

0.0

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.025

T;T

Eigen

Uncertain

0.39

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.88

D;D

M_CAP

Benign

0.051

MetaRNN

Benign

0.34

T;T

MetaSVM

Benign

-0.76

MutationAssessor

Uncertain

2.6

M;.

MutationTaster

Benign

0.81

D;D;D;D

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-0.12

N;N

REVEL

Benign

0.21

Sift

Uncertain

0.028

D;D

Sift4G

Benign

0.20

T;T

Polyphen

0.87

P;.

Vest4

0.67

MutPred

0.33

Loss of stability (P = 0.0263);Loss of stability (P = 0.0263);

MVP

0.78

MPC

0.19

ClinPred

0.90

GERP RS

5.3

Varity_R

0.20

gMVP

0.32

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.44

dbscSNV1_RF

Benign

0.34

SpliceAI score (max)

0.17

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over