rs546992311

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7

The NM_001164507.2(NEB):c.16449C>T(p.Ser5483Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0023 ( 6 hom., cov: 8)

Exomes 𝑓: 0.0019 ( 61 hom. )

Failed GnomAD Quality Control

Consequence

NEB
NM_001164507.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.303

Publications

0 publications found

Variant links:

Genes affected

NEB (HGNC:7720): (nebulin) This gene encodes nebulin, a giant protein component of the cytoskeletal matrix that coexists with the thick and thin filaments within the sarcomeres of skeletal muscle. In most vertebrates, nebulin accounts for 3 to 4% of the total myofibrillar protein. The encoded protein contains approximately 30-amino acid long modules that can be classified into 7 types and other repeated modules. Protein isoform sizes vary from 600 to 800 kD due to alternative splicing that is tissue-, species-,and developmental stage-specific. Of the 183 exons in the nebulin gene, at least 43 are alternatively spliced, although exons 143 and 144 are not found in the same transcript. Of the several thousand transcript variants predicted for nebulin, the RefSeq Project has decided to create three representative RefSeq records. Mutations in this gene are associated with recessive nemaline myopathy. [provided by RefSeq, Sep 2009]

NEB Gene-Disease associations (from GenCC):

nemaline myopathy 2
Inheritance: AR, AD Classification: DEFINITIVE, STRONG, LIMITED Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Myriad Women’s Health, G2P, Ambry Genetics
childhood-onset nemaline myopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
intermediate nemaline myopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
typical nemaline myopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
lethal multiple pterygium syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
severe congenital nemaline myopathy
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

NEB links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 2-151579593-G-A is Benign according to our data. Variant chr2-151579593-G-A is described in ClinVar as Benign. ClinVar VariationId is 257761.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.303 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001164507.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
NEB	NM_001164507.2	MANE Plus Clinical	c.16449C>T	p.Ser5483Ser	synonymous	Exon 105 of 182	NP_001157979.2
NEB	NM_001164508.2	MANE Select	c.16449C>T	p.Ser5483Ser	synonymous	Exon 105 of 182	NP_001157980.2
NEB	NM_001271208.2		c.16449C>T	p.Ser5483Ser	synonymous	Exon 105 of 183	NP_001258137.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
NEB	ENST00000397345.8	TSL:5 MANE Select	c.16449C>T	p.Ser5483Ser	synonymous	Exon 105 of 182	ENSP00000380505.3
NEB	ENST00000427231.7	TSL:5 MANE Plus Clinical	c.16449C>T	p.Ser5483Ser	synonymous	Exon 105 of 182	ENSP00000416578.2
NEB	ENST00000413693.5	TSL:5	c.639C>T	p.Ser213Ser	synonymous	Exon 5 of 74	ENSP00000410961.1

Frequencies

GnomAD3 genomes

AF:

0.00235

AC:

152

AN:

64802

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000386

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00557

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0560

Gnomad SAS

AF:

0.00449

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000109

Gnomad OTH

AF:

0.00391

GnomAD2 exomes

AF:

0.0139

AC:

551

AN:

39680

AF XY:

0.0138

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0153

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0697

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000373

Gnomad OTH exome

AF:

0.00893

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00191

AC:

2047

AN:

1072496

Hom.:

Cov.:

AF XY:

0.00189

AC XY:

1020

AN XY:

539308

show subpopulations

African (AFR)

AF:

0.000579

AC:

AN:

27638

American (AMR)

AF:

0.00926

AC:

324

AN:

35008

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23520

East Asian (EAS)

AF:

0.0328

AC:

1119

AN:

34122

South Asian (SAS)

AF:

0.00392

AC:

291

AN:

74186

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47340

Middle Eastern (MID)

AF:

0.000279

AC:

AN:

3582

European-Non Finnish (NFE)

AF:

0.0000937

AC:

AN:

779486

Other (OTH)

AF:

0.00468

AC:

223

AN:

47614

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.580

Heterozygous variant carriers

124

186

248

310

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

102

136

170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00230

AC:

149

AN:

64922

Hom.:

Cov.:

AF XY:

0.00249

AC XY:

AN XY:

29738

show subpopulations

African (AFR)

AF:

0.000385

AC:

AN:

23390

American (AMR)

AF:

0.00557

AC:

AN:

4130

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1988

East Asian (EAS)

AF:

0.0539

AC:

102

AN:

1894

South Asian (SAS)

AF:

0.00450

AC:

AN:

1778

European-Finnish (FIN)

AF:

0.00

AC:

AN:

2786

Middle Eastern (MID)

AF:

0.00

AC:

AN:

164

European-Non Finnish (NFE)

AF:

0.000109

AC:

AN:

27470

Other (OTH)

AF:

0.00505

AC:

AN:

792

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.580

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00160

Hom.:

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (2)

Nemaline myopathy 2 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

8.7

(source)

DANN

Benign

0.61

PhyloP100

-0.30

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over