rs1442801795

Variant names:

• chr10-20889861-C-A
• rs1442801795
• NM_006393.3:c.242G>T

Your query was ambiguous. Multiple possible variants found:

• chr10-20889861-C-A
• chr10-20889861-C-G
• chr10-20889861-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006393.3(NEBL):​c.242G>T​(p.Gly81Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,458,078 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict 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. G81S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: NEBL NM_006393.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.65
• Publications: 0 publications found

Genes affected

NEBL (HGNC:16932): (nebulette) This gene encodes a nebulin like protein that is abundantly expressed in cardiac muscle. The encoded protein binds actin and interacts with thin filaments and Z-line associated proteins in striated muscle. This protein may be involved in cardiac myofibril assembly. A shorter isoform of this protein termed LIM nebulette is expressed in non-muscle cells and may function as a component of focal adhesion complexes. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Mar 2010]

NEBL Gene-Disease associations (from GenCC):

• dilated cardiomyopathy

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16221577).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEBL	NM_006393.3	c.242G>T	p.Gly81Val	missense_variant	Exon 3 of 28	ENST00000377122.9	NP_006384.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEBL	ENST00000377122.9	c.242G>T	p.Gly81Val	missense_variant	Exon 3 of 28	1	NM_006393.3	ENSP00000366326.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1458078 Hom.: 0 Cov.: 28 AF XY: 0.00000138 AC XY: 1 AN XY: 725636

African (AFR) AF: 0.00 AC: 0 AN: 33380

American (AMR) AF: 0.00 AC: 0 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26110

East Asian (EAS) AF: 0.00 AC: 0 AN: 39614

South Asian (SAS) AF: 0.00 AC: 0 AN: 86126

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00000271 AC: 3 AN: 1108686

Other (OTH) AF: 0.00 AC: 0 AN: 60274

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Benign	-0.036	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.024	T;T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.056
FATHMM_MKL	Benign	0.18	N
LIST_S2	Uncertain	0.86	D;D
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M;.
PhyloP100		1.6
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-2.9	D;D
REVEL	Benign	0.15
Sift	Benign	0.11	T;T
Sift4G	Uncertain	0.045	D;.
Polyphen		0.070	B;.
Vest4		0.67
MutPred		0.46		Loss of helix (P = 0.0558);.;
MVP		0.51
MPC		0.034
ClinPred		0.65	D
GERP RS		6.2
Varity_R		0.16
gMVP		0.50
Mutation Taster		=92/8	polymorphism

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

Other links and lift over

dbSNP: rs1442801795; hg19: chr10-21178790;