rs182998780

Positions:

• chr1-77942586-C-G
• chr1-77942586-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_144573.4(NEXN):​c.1785C>G​(p.Asp595Glu) variant causes a missense 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D595G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NEXN NM_144573.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.430

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]

ACMG classification

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=0.41744983).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEXN	NM_144573.4	c.1785C>G	p.Asp595Glu	missense_variant	13/13	ENST00000334785.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEXN	ENST00000334785.12	c.1785C>G	p.Asp595Glu	missense_variant	13/13	1	NM_144573.4	P3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.56
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0078	.;T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.62	D
LIST_S2	Uncertain	0.97	D;D
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.42	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.28	.;N
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-0.52	N;N
REVEL	Benign	0.20
Sift	Benign	0.18	T;T
Sift4G	Uncertain	0.028	D;D
Polyphen		1.0	.;D
Vest4		0.68
MutPred		0.31		.;Gain of disorder (P = 0.0838);
MVP		0.21
MPC		0.29
ClinPred		0.85	D
GERP RS		-0.29
Varity_R		0.10
gMVP		0.29

Splicing

Name	Calibrated prediction	Score	Prediction
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

LitVar

Other links and lift over

dbSNP: rs182998780; hg19: chr1-78408271;