15-99129955-C-T

Variant names:

• chr15-99129955-C-T
• NM_145728.3:c.1595C>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_145728.3(SYNM):​c.1595C>T​(p.Ser532Phe) 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. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SYNM NM_145728.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.870

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)

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24211559).
• BP6: Variant 15-99129955-C-T is Benign according to our data. Variant chr15-99129955-C-T is described in ClinVar as [Benign]. Clinvar id is 3035351.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNM	NM_145728.3	c.1595C>T	p.Ser532Phe	missense_variant	Exon 4 of 4	ENST00000336292.11	NP_663780.2
SYNM	NM_015286.6	c.1595C>T	p.Ser532Phe	missense_variant	Exon 4 of 5		NP_056101.5
SYNM	XM_017022035.2	c.1595C>T	p.Ser532Phe	missense_variant	Exon 4 of 5		XP_016877524.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYNM	ENST00000336292.11	c.1595C>T	p.Ser532Phe	missense_variant	Exon 4 of 4	1	NM_145728.3	ENSP00000336775.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

SYNM-related disorder Benign:1

May 17, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as 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	Pathogenic	0.84
BayesDel_addAF	Uncertain	0.021	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.037	.;.;T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Benign	0.53	D
LIST_S2	Uncertain	0.86	D;.;D
M_CAP	Benign	0.069	D
MetaRNN	Benign	0.24	T;T;T
MetaSVM	Benign	-0.74	T
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-2.7	D;.;.
REVEL	Benign	0.17
Sift	Uncertain	0.0010	D;.;.
Sift4G	Uncertain	0.0040	D;D;D
Vest4		0.55
MutPred		0.17		.;Loss of phosphorylation at S532 (P = 0.0016);Loss of phosphorylation at S532 (P = 0.0016);
MVP		0.54
MPC		0.69
ClinPred		0.93	D
GERP RS		5.8
gMVP		0.36

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: chr15-99670160; COSMIC: COSV60371225;