Genetic Variant SYNM:p.Gly83Asp (chr15-99105447-G-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_145728.3(SYNM):c.248G>A(p.Gly83Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000328 in 1,432,718 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

SYNM
NM_145728.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.443

Publications

0 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.14485568).

BS2

High AC in GnomAd4 at 10 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145728.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SYNM	NM_145728.3	MANE Select	c.248G>A	p.Gly83Asp	missense	Exon 1 of 4	NP_663780.2	O15061-1
SYNM	NM_015286.6		c.248G>A	p.Gly83Asp	missense	Exon 1 of 5	NP_056101.5
SYNM-AS1	NR_187219.1		n.190+241C>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SYNM	ENST00000336292.11	TSL:1 MANE Select	c.248G>A	p.Gly83Asp	missense	Exon 1 of 4	ENSP00000336775.7	O15061-1
SYNM	ENST00000594047.2	TSL:1	c.248G>A	p.Gly83Asp	missense	Exon 1 of 5	ENSP00000472953.1	O15061-2
SYNM	ENST00000328642.11	TSL:1	c.248G>A	p.Gly83Asp	missense	Exon 1 of 4	ENSP00000330469.8	O15061-3

Frequencies

GnomAD3 genomes

AF:

0.0000659

AC:

AN:

151702

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00174

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000479

GnomAD2 exomes

AF:

0.000132

AC:

AN:

60382

AF XY:

0.0000841

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00489

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000558

GnomAD4 exome

AF:

0.0000289

AC:

AN:

1280910

Hom.:

Cov.:

AF XY:

0.0000254

AC XY:

AN XY:

630698

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25398

American (AMR)

AF:

0.00

AC:

AN:

21278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21452

East Asian (EAS)

AF:

0.00103

AC:

AN:

28022

South Asian (SAS)

AF:

0.00

AC:

AN:

66132

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31540

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3738

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1030668

Other (OTH)

AF:

0.000152

AC:

AN:

52682

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.520

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

AF:

0.0000659

AC:

AN:

151808

Hom.:

Cov.:

AF XY:

0.0000943

AC XY:

AN XY:

74220

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41484

American (AMR)

AF:

0.00

AC:

AN:

15248

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00175

AC:

AN:

5156

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10410

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67900

Other (OTH)

AF:

0.000474

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.520

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.00

Hom.:

Bravo

AF:

0.0000680

Asia WGS

AF:

0.000291

AC:

AN:

3450

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Uncertain

-0.030

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.38

Eigen

Benign

0.014

Eigen_PC

Benign

-0.14

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.66

M_CAP

Pathogenic

0.93

MetaRNN

Benign

0.14

MetaSVM

Uncertain

0.52

PhyloP100

0.44

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-1.4

REVEL

Uncertain

0.55

Sift

Uncertain

0.013

Sift4G

Benign

0.58

Polyphen

1.0

Vest4

0.44

MutPred

0.37

Loss of MoRF binding (P = 0.0376)

MVP

0.80

MPC

0.64

ClinPred

0.10

GERP RS

3.6

PromoterAI

-0.00060

Neutral

(source)

gMVP

0.38

Mutation Taster

=91/9

polymorphism

(source)

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

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

Computational scores

Splicing

Publications

Other links and lift over