Variant 15-99105416-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_145728.3(SYNM):c.217G>C(p.Glu73Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00476 in 1,506,676 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0030 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0050 ( 24 hom. )

Consequence

SYNM
NM_145728.3 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.11

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 -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0060783923).

BP6

Variant 15-99105416-G-C is Benign according to our data. Variant chr15-99105416-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 3053288.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 463 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYNM	NM_145728.3 linkuse as main transcript	c.217G>C	p.Glu73Gln	missense_variant	1/4	ENST00000336292.11	NP_663780.2
SYNM-AS1	XR_001751810.2 linkuse as main transcript	n.84+2389C>G		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.217G>C	p.Glu73Gln	missense_variant	1/4	1	NM_145728.3	ENSP00000336775	P3	O15061-1
SYNM-AS1	ENST00000559468.1 linkuse as main transcript	n.137+272C>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes

AF:

0.00305

AC:

463

AN:

151862

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000846

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00236

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00248

Gnomad FIN

AF:

0.00143

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00528

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00284

AC:

302

AN:

106178

Hom.:

AF XY:

0.00302

AC XY:

179

AN XY:

59220

show subpopulations

Gnomad AFR exome

AF:

0.000433

Gnomad AMR exome

AF:

0.00138

Gnomad ASJ exome

AF:

0.000148

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00298

Gnomad FIN exome

AF:

0.00205

Gnomad NFE exome

AF:

0.00471

Gnomad OTH exome

AF:

0.00302

GnomAD4 exome

AF:

0.00495

AC:

6710

AN:

1354704

Hom.:

Cov.:

AF XY:

0.00488

AC XY:

3260

AN XY:

668276

show subpopulations

Gnomad4 AFR exome

AF:

0.000573

Gnomad4 AMR exome

AF:

0.00153

Gnomad4 ASJ exome

AF:

0.000127

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00353

Gnomad4 FIN exome

AF:

0.00156

Gnomad4 NFE exome

AF:

0.00577

Gnomad4 OTH exome

AF:

0.00275

GnomAD4 genome

AF:

0.00305

AC:

463

AN:

151972

Hom.:

Cov.:

AF XY:

0.00291

AC XY:

216

AN XY:

74296

show subpopulations

Gnomad4 AFR

AF:

0.000844

Gnomad4 AMR

AF:

0.00236

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00248

Gnomad4 FIN

AF:

0.00143

Gnomad4 NFE

AF:

0.00528

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00338

Hom.:

Bravo

AF:

0.00280

ExAC

AF:

0.00167

AC:

Asia WGS

AF:

0.000290

AC:

AN:

3458

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SYNM-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 28, 2019

This variant is classified as likely 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

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.26

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.22

.;T;T

Eigen

Benign

0.0094

Eigen_PC

Benign

-0.041

FATHMM_MKL

Benign

0.51

LIST_S2

Benign

0.67

.;T;T

MetaRNN

Benign

0.0061

T;T;T

MetaSVM

Uncertain

0.36

MutationTaster

Benign

0.98

D;D;D

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-0.32

N;N;.

REVEL

Uncertain

0.35

Sift

Benign

0.21

T;T;.

Sift4G

Uncertain

0.018

D;T;D

Polyphen

0.97

.;D;.

Vest4

0.24

MVP

0.69

MPC

0.63

ClinPred

0.032

GERP RS

3.6

gMVP

0.31

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