Variant chr15-99105607-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_145728.3(SYNM):c.408G>A(p.Arg136=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.342 in 1,262,182 control chromosomes in the GnomAD database, including 77,031 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.41 ( 13668 hom., cov: 32)

Exomes 𝑓: 0.33 ( 63363 hom. )

Consequence

SYNM
NM_145728.3 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.196

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 made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP6

Variant 15-99105607-G-A is Benign according to our data. Variant chr15-99105607-G-A is described in ClinVar as [Benign]. Clinvar id is 3034822.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.196 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.597 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYNM	NM_145728.3 linkuse as main transcript	c.408G>A	p.Arg136=	synonymous_variant	1/4	ENST00000336292.11	NP_663780.2
SYNM-AS1	XR_001751810.2 linkuse as main transcript	n.84+2198C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYNM	ENST00000336292.11 linkuse as main transcript	c.408G>A	p.Arg136=	synonymous_variant	1/4	1	NM_145728.3	ENSP00000336775	P3	O15061-1
SYNM-AS1	ENST00000559468.1 linkuse as main transcript	n.137+81C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes

AF:

0.411

AC:

60984

AN:

148250

Hom.:

13635

Cov.:

show subpopulations

Gnomad AFR

AF:

0.603

Gnomad AMI

AF:

0.439

Gnomad AMR

AF:

0.350

Gnomad ASJ

AF:

0.391

Gnomad EAS

AF:

0.388

Gnomad SAS

AF:

0.380

Gnomad FIN

AF:

0.308

Gnomad MID

AF:

0.302

Gnomad NFE

AF:

0.328

Gnomad OTH

AF:

0.403

GnomAD3 exomes

AF:

0.235

AC:

1345

AN:

5726

Hom.:

166

AF XY:

0.237

AC XY:

850

AN XY:

3592

show subpopulations

Gnomad AFR exome

AF:

0.438

Gnomad AMR exome

AF:

0.235

Gnomad ASJ exome

AF:

0.260

Gnomad EAS exome

AF:

0.261

Gnomad SAS exome

AF:

0.255

Gnomad FIN exome

AF:

0.178

Gnomad NFE exome

AF:

0.226

Gnomad OTH exome

AF:

0.211

GnomAD4 exome

AF:

0.332

AC:

369988

AN:

1113828

Hom.:

63363

Cov.:

AF XY:

0.332

AC XY:

178027

AN XY:

536438

show subpopulations

Gnomad4 AFR exome

AF:

0.618

Gnomad4 AMR exome

AF:

0.311

Gnomad4 ASJ exome

AF:

0.372

Gnomad4 EAS exome

AF:

0.483

Gnomad4 SAS exome

AF:

0.354

Gnomad4 FIN exome

AF:

0.302

Gnomad4 NFE exome

AF:

0.321

Gnomad4 OTH exome

AF:

0.340

GnomAD4 genome

AF:

0.412

AC:

61067

AN:

148354

Hom.:

13668

Cov.:

AF XY:

0.409

AC XY:

29554

AN XY:

72288

show subpopulations

Gnomad4 AFR

AF:

0.603

Gnomad4 AMR

AF:

0.350

Gnomad4 ASJ

AF:

0.391

Gnomad4 EAS

AF:

0.388

Gnomad4 SAS

AF:

0.380

Gnomad4 FIN

AF:

0.308

Gnomad4 NFE

AF:

0.328

Gnomad4 OTH

AF:

0.402

Alfa

AF:

0.207

Hom.:

390

Bravo

AF:

0.420

Asia WGS

AF:

0.380

AC:

1226

AN:

3228

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SYNM-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 28, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

9.4

DANN

Benign

0.93

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over