15-99130271-C-T
Variant names:
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2
The NM_145728.3(SYNM):c.1911C>T(p.Thr637Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000564 in 1,613,952 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 Likely benign (★).
Frequency
Genomes: 𝑓 0.000085 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000053 ( 0 hom. )
Consequence
SYNM
NM_145728.3 synonymous
NM_145728.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.361
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.56).
BP6
Variant 15-99130271-C-T is Benign according to our data. Variant chr15-99130271-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 764186.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.361 with no splicing effect.
BS2
High AC in GnomAd4 at 13 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SYNM | NM_145728.3 | c.1911C>T | p.Thr637Thr | synonymous_variant | Exon 4 of 4 | ENST00000336292.11 | NP_663780.2 | |
SYNM | NM_015286.6 | c.1911C>T | p.Thr637Thr | synonymous_variant | Exon 4 of 5 | NP_056101.5 | ||
SYNM | XM_017022035.2 | c.1911C>T | p.Thr637Thr | synonymous_variant | Exon 4 of 5 | XP_016877524.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000854 AC: 13AN: 152166Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000149 AC: 37AN: 249084Hom.: 0 AF XY: 0.000155 AC XY: 21AN XY: 135156
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GnomAD4 exome AF: 0.0000534 AC: 78AN: 1461668Hom.: 0 Cov.: 36 AF XY: 0.0000688 AC XY: 50AN XY: 727112
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GnomAD4 genome AF: 0.0000854 AC: 13AN: 152284Hom.: 0 Cov.: 32 AF XY: 0.0000940 AC XY: 7AN XY: 74464
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Aug 21, 2018
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
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Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at