Genetic Variant SYNM:p.Ala115Val (chr15-99105543-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_145728.3(SYNM):c.344C>T(p.Ala115Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000118 in 1,214,544 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00010 ( 0 hom. )

Consequence

SYNM
NM_145728.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.524

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: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.04391727).

BS2

High AC in GnomAd4 at 33 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.344C>T	p.Ala115Val	missense	Exon 1 of 4	NP_663780.2	O15061-1
SYNM	NM_015286.6		c.344C>T	p.Ala115Val	missense	Exon 1 of 5	NP_056101.5
SYNM-AS1	NR_187219.1		n.190+145G>A		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SYNM	ENST00000336292.11	TSL:1 MANE Select	c.344C>T	p.Ala115Val	missense	Exon 1 of 4	ENSP00000336775.7	O15061-1
SYNM	ENST00000594047.2	TSL:1	c.344C>T	p.Ala115Val	missense	Exon 1 of 5	ENSP00000472953.1	O15061-2
SYNM	ENST00000328642.11	TSL:1	c.344C>T	p.Ala115Val	missense	Exon 1 of 4	ENSP00000330469.8	O15061-3

Frequencies

GnomAD3 genomes

AF:

0.000221

AC:

AN:

149202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000665

Gnomad ASJ

AF:

0.00817

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000598

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000600

AC:

AN:

3334

AF XY:

0.000912

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00397

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000548

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000103

AC:

110

AN:

1065342

Hom.:

Cov.:

AF XY:

0.000100

AC XY:

AN XY:

508916

show subpopulations

African (AFR)

AF:

0.0000468

AC:

AN:

21366

American (AMR)

AF:

0.000269

AC:

AN:

7432

Ashkenazi Jewish (ASJ)

AF:

0.00563

AC:

AN:

12622

East Asian (EAS)

AF:

0.00

AC:

AN:

22322

South Asian (SAS)

AF:

0.0000405

AC:

AN:

24718

European-Finnish (FIN)

AF:

0.00

AC:

AN:

20586

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2760

European-Non Finnish (NFE)

AF:

0.0000208

AC:

AN:

912220

Other (OTH)

AF:

0.000387

AC:

AN:

41316

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.543

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:

0.000221

AC:

AN:

149202

Hom.:

Cov.:

AF XY:

0.000220

AC XY:

AN XY:

72748

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41072

American (AMR)

AF:

0.0000665

AC:

AN:

15030

Ashkenazi Jewish (ASJ)

AF:

0.00817

AC:

AN:

3426

East Asian (EAS)

AF:

0.00

AC:

AN:

5130

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9532

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000598

AC:

AN:

66908

Other (OTH)

AF:

0.00

AC:

AN:

2052

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

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:

0.000214

Hom.:

Bravo

AF:

0.000144

ExAC

AF:

0.00132

AC:

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

0.13

BayesDel_addAF

Benign

-0.043

BayesDel_noAF

Benign

-0.30

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.43

Eigen

Benign

0.11

Eigen_PC

Benign

-0.025

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.79

M_CAP

Pathogenic

0.99

MetaRNN

Benign

0.044

MetaSVM

Uncertain

0.30

PhyloP100

-0.52

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-1.9

REVEL

Uncertain

0.44

Sift

Uncertain

0.0090

Sift4G

Uncertain

0.054

Polyphen

0.99

Vest4

0.21

MutPred

0.46

Gain of MoRF binding (P = 0.146)

MVP

0.88

MPC

0.56

ClinPred

0.26

GERP RS

3.6

PromoterAI

-0.0094

Neutral

(source)

gMVP

0.41

Mutation Taster

=92/8

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