15-99129767-C-T

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_145728.3(SYNM):​c.1407C>T​(p.Arg469Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000816 in 1,613,456 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0039 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00049 ( 3 hom. )

Consequence

SYNM
NM_145728.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -3.45
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)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.7).
BP6
Variant 15-99129767-C-T is Benign according to our data. Variant chr15-99129767-C-T is described in ClinVar as [Benign]. Clinvar id is 718202.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-3.45 with no splicing effect.
BS2
High AC in GnomAd4 at 599 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SYNMNM_145728.3 linkc.1407C>T p.Arg469Arg synonymous_variant Exon 4 of 4 ENST00000336292.11 NP_663780.2 O15061-1
SYNMNM_015286.6 linkc.1407C>T p.Arg469Arg synonymous_variant Exon 4 of 5 NP_056101.5 O15061-2A0A075B7B1
SYNMXM_017022035.2 linkc.1407C>T p.Arg469Arg synonymous_variant Exon 4 of 5 XP_016877524.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SYNMENST00000336292.11 linkc.1407C>T p.Arg469Arg synonymous_variant Exon 4 of 4 1 NM_145728.3 ENSP00000336775.7 O15061-1

Frequencies

GnomAD3 genomes
AF:
0.00394
AC:
599
AN:
152064
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0135
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00164
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000208
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.0000735
Gnomad OTH
AF:
0.00382
GnomAD3 exomes
AF:
0.00129
AC:
321
AN:
248774
Hom.:
2
AF XY:
0.00107
AC XY:
145
AN XY:
135044
show subpopulations
Gnomad AFR exome
AF:
0.0147
Gnomad AMR exome
AF:
0.00223
Gnomad ASJ exome
AF:
0.0000995
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000980
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000887
Gnomad OTH exome
AF:
0.000662
GnomAD4 exome
AF:
0.000491
AC:
717
AN:
1461274
Hom.:
3
Cov.:
30
AF XY:
0.000450
AC XY:
327
AN XY:
726918
show subpopulations
Gnomad4 AFR exome
AF:
0.0139
Gnomad4 AMR exome
AF:
0.00206
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.000104
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000477
Gnomad4 OTH exome
AF:
0.00149
GnomAD4 genome
AF:
0.00394
AC:
599
AN:
152182
Hom.:
1
Cov.:
32
AF XY:
0.00379
AC XY:
282
AN XY:
74384
show subpopulations
Gnomad4 AFR
AF:
0.0135
Gnomad4 AMR
AF:
0.00164
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000208
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000735
Gnomad4 OTH
AF:
0.00378
Alfa
AF:
0.000679
Hom.:
0
Bravo
AF:
0.00486
Asia WGS
AF:
0.00231
AC:
8
AN:
3478
EpiCase
AF:
0.00
EpiControl
AF:
0.000119

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Dec 31, 2019
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.70
CADD
Benign
0.26
DANN
Benign
0.80

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs77306380; hg19: chr15-99669972; COSMIC: COSV60369247; API