chr15-99130270-C-T

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4BP6_Moderate

The NM_145728.3(SYNM):​c.1910C>T​(p.Thr637Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. T637T) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Consequence

SYNM
NM_145728.3 missense

Scores

4
14

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.47
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-AS2 (HGNC:56228): (SYNM antisense RNA 2)

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.365449).
BP6
Variant 15-99130270-C-T is Benign according to our data. Variant chr15-99130270-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3032040.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SYNMNM_145728.3 linkc.1910C>T p.Thr637Ile missense_variant Exon 4 of 4 ENST00000336292.11 NP_663780.2 O15061-1
SYNMNM_015286.6 linkc.1910C>T p.Thr637Ile missense_variant Exon 4 of 5 NP_056101.5 O15061-2A0A075B7B1
SYNMXM_017022035.2 linkc.1910C>T p.Thr637Ile missense_variant Exon 4 of 5 XP_016877524.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SYNMENST00000336292.11 linkc.1910C>T p.Thr637Ile missense_variant Exon 4 of 4 1 NM_145728.3 ENSP00000336775.7 O15061-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
36
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

SYNM-related disorder Benign:1
Jan 21, 2021
PreventionGenetics, part of Exact Sciences
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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
0.34
BayesDel_addAF
Benign
-0.076
T
BayesDel_noAF
Benign
-0.35
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.044
.;.;T
Eigen
Benign
-0.27
Eigen_PC
Benign
-0.41
FATHMM_MKL
Benign
0.19
N
LIST_S2
Benign
0.78
T;.;T
M_CAP
Benign
0.043
D
MetaRNN
Benign
0.37
T;T;T
MetaSVM
Benign
-0.93
T
PrimateAI
Benign
0.38
T
PROVEAN
Uncertain
-2.6
D;.;.
REVEL
Benign
0.15
Sift
Uncertain
0.0030
D;.;.
Sift4G
Uncertain
0.011
D;D;D
Vest4
0.55
MutPred
0.25
.;Gain of loop (P = 0.0195);Gain of loop (P = 0.0195);
MVP
0.29
MPC
0.67
ClinPred
0.84
D
GERP RS
2.9
gMVP
0.29

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.

Other links and lift over

hg19: chr15-99670475; API