dbSNP rs1405694567: SYNM:p.Asp110Glu (chr15-99105529-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_145728.3(SYNM):c.330C>A(p.Asp110Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000909 in 1,100,534 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D110N) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 9.1e-7 ( 0 hom. )

Consequence

SYNM
NM_145728.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.667

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 Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.28008255).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNM	NM_145728.3 link	c.330C>A	p.Asp110Glu	missense_variant	Exon 1 of 4	ENST00000336292.11	NP_663780.2	O15061-1
SYNM	NM_015286.6 link	c.330C>A	p.Asp110Glu	missense_variant	Exon 1 of 5		NP_056101.5	O15061-2A0A075B7B1
SYNM	XM_017022035.2 link	c.330C>A	p.Asp110Glu	missense_variant	Exon 1 of 5		XP_016877524.1
SYNM-AS1	NR_187219.1 link	n.190+159G>T		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYNM	ENST00000336292.11 link	c.330C>A	p.Asp110Glu	missense_variant	Exon 1 of 4	1	NM_145728.3	ENSP00000336775.7		O15061-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.09e-7

AC:

AN:

1100534

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

529618

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000107

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.22

.;T;T

Eigen

Benign

-0.92

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.030

LIST_S2

Benign

0.56

.;T;T

M_CAP

Pathogenic

0.95

MetaRNN

Benign

0.28

T;T;T

MetaSVM

Benign

-0.71

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

0.080

N;N;.

REVEL

Uncertain

0.31

Sift

Benign

0.56

T;T;.

Sift4G

Benign

1.0

T;T;T

Polyphen

1.0

.;D;.

Vest4

0.090

MutPred

0.49

Gain of methylation at R108 (P = 0.1132);Gain of methylation at R108 (P = 0.1132);Gain of methylation at R108 (P = 0.1132);

MVP

0.68

MPC

0.55

ClinPred

0.33

GERP RS

-2.6

gMVP

0.22

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over