Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 2P and 8B. PM2BP6_Very_Strong

The ENST00000336292.11(SYNM):c.703dupG(p.Glu235GlyfsTer40) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Benign (★★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 33)

Consequence

SYNM
ENST00000336292.11 frameshift

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.51

Publications

11 publications found

Variant links:

Genes affected

SYNM (HGNC:24466): (synemin) The protein encoded by this gene is an intermediate filament (IF) family member. IF proteins are cytoskeletal proteins that confer resistance to mechanical stress and are encoded by a dispersed multigene family. This protein has been found to form a linkage between desmin, which is a subunit of the IF network, and the extracellular matrix, and provides an important structural support in muscle. Two alternatively spliced variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

SYNM links:

SYNM-AS1 (HGNC:55421): (SYNM antisense RNA 1)

SYNM-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP6

Variant 15-99105901-A-AG is Benign according to our data. Variant chr15-99105901-A-AG is described in ClinVar as Benign. ClinVar VariationId is 403504.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000336292.11. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SYNM	NM_145728.3	MANE Select	c.703dupG	p.Glu235GlyfsTer40	frameshift	Exon 1 of 4	NP_663780.2
SYNM	NM_015286.6		c.703dupG	p.Glu235GlyfsTer40	frameshift	Exon 1 of 5	NP_056101.5
SYNM-AS1	NR_187219.1		n.-25dupC		upstream_gene	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SYNM	ENST00000336292.11	TSL:1 MANE Select	c.703dupG	p.Glu235GlyfsTer40	frameshift	Exon 1 of 4	ENSP00000336775.7
SYNM	ENST00000594047.2	TSL:1	c.703dupG	p.Glu235GlyfsTer40	frameshift	Exon 1 of 5	ENSP00000472953.1
SYNM	ENST00000328642.11	TSL:1	c.703dupG	p.Glu235GlyfsTer40	frameshift	Exon 1 of 4	ENSP00000330469.8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

1.00

AC:

131290

AN:

131292

AF XY:

1.00

show subpopulations

Gnomad AFR exome

AF:

1.00

Gnomad AMR exome

AF:

1.00

Gnomad ASJ exome

AF:

1.00

Gnomad EAS exome

AF:

1.00

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

1.00

Gnomad OTH exome

AF:

1.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

1.00

Hom.:

6701

Asia WGS

AF:

0.999

AC:

3445

AN:

3450

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

SYNM-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

3.5

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over