rs371551337

Variant names:

• chr10-20817647-G-A
• NM_006393.3:c.2101C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-20817647-G-A
• chr10-20817647-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006393.3(NEBL):​c.2101C>T​(p.Pro701Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,680 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: NEBL NM_006393.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.590

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1236428).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEBL	NM_006393.3	c.2101C>T	p.Pro701Ser	missense_variant	Exon 21 of 28	ENST00000377122.9	NP_006384.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEBL	ENST00000377122.9	c.2101C>T	p.Pro701Ser	missense_variant	Exon 21 of 28	1	NM_006393.3	ENSP00000366326.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461680 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727156

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	18
DANN	Benign	0.64
DEOGEN2	Benign	0.0020	T;T
Eigen	Benign	-0.069
Eigen_PC	Benign	0.059
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.86	D;D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L;.
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.34	N;.
REVEL	Benign	0.063
Sift	Benign	0.65	T;.
Sift4G	Benign	0.71	T;T
Polyphen		0.18	B;.
Vest4		0.48
MutPred		0.43		Loss of catalytic residue at P701 (P = 0.0017);.;
MVP		0.52
MPC		0.036
ClinPred		0.38	T
GERP RS		5.0
Varity_R		0.076
gMVP		0.14

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-21106576; COSMIC: COSV105317858; COSMIC: COSV105317858;