1-32695338-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_030786.3(SYNC):​c.760G>A​(p.Val254Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000643 in 1,399,746 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 28)
Exomes 𝑓: 0.0000064 ( 0 hom. )

Consequence

SYNC
NM_030786.3 missense

Scores

12
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.33
Variant links:
Genes affected
SYNC (HGNC:28897): (syncoilin, intermediate filament protein) This gene encodes a member of the intermediate filament family which contains an N-terminal head domain, followed by a central coiled-coil region and a short C-terminal tail. The protein is highly expressed in skeletal and cardiac muscle. The protein links the dystrophin associated protein complex (DAPC) to desmin filaments in muscle and may have a structural role in striated muscle. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2009]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SYNCNM_030786.3 linkc.760G>A p.Val254Met missense_variant Exon 2 of 5 ENST00000409190.8 NP_110413.3 Q9H7C4-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SYNCENST00000409190.8 linkc.760G>A p.Val254Met missense_variant Exon 2 of 5 2 NM_030786.3 ENSP00000386439.3 Q9H7C4-1
SYNCENST00000373484.4 linkc.760G>A p.Val254Met missense_variant Exon 2 of 4 2 ENSP00000362583.3 Q9H7C4-2
SYNCENST00000417633.1 linkc.*227G>A downstream_gene_variant 4 ENSP00000401975.1 C9JSS1

Frequencies

GnomAD3 genomes
Cov.:
28
GnomAD4 exome
AF:
0.00000643
AC:
9
AN:
1399746
Hom.:
0
Cov.:
98
AF XY:
0.00000724
AC XY:
5
AN XY:
690378
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:
0.00000556
Gnomad4 OTH exome
AF:
0.0000344
GnomAD4 genome
Cov.:
28

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 02, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.760G>A (p.V254M) alteration is located in exon 2 (coding exon 2) of the SYNC gene. This alteration results from a G to A substitution at nucleotide position 760, causing the valine (V) at amino acid position 254 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.49
BayesDel_addAF
Uncertain
0.069
T
BayesDel_noAF
Benign
-0.14
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.22
T;.
Eigen
Uncertain
0.37
Eigen_PC
Uncertain
0.37
FATHMM_MKL
Uncertain
0.81
D
LIST_S2
Uncertain
0.93
D;D
M_CAP
Benign
0.058
D
MetaRNN
Uncertain
0.43
T;T
MetaSVM
Uncertain
0.14
D
MutationAssessor
Benign
0.81
L;L
PrimateAI
Uncertain
0.67
T
PROVEAN
Benign
-0.92
N;N
REVEL
Uncertain
0.39
Sift
Uncertain
0.022
D;D
Sift4G
Benign
0.13
T;T
Polyphen
1.0
D;D
Vest4
0.45
MutPred
0.45
Gain of MoRF binding (P = 0.102);Gain of MoRF binding (P = 0.102);
MVP
0.69
MPC
1.0
ClinPred
0.88
D
GERP RS
3.5
Varity_R
0.17
gMVP
0.16

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: chr1-33160939; API