NM_030786.3:c.1147C>G

Variant names:

• chr1-32694951-G-C
• NM_030786.3:c.1147C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_030786.3(SYNC):​c.1147C>G​(p.Arg383Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,796 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R383W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SYNC NM_030786.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.46

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14491808).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNC	NM_030786.3	c.1147C>G	p.Arg383Gly	missense_variant	Exon 2 of 5	ENST00000409190.8	NP_110413.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYNC	ENST00000409190.8	c.1147C>G	p.Arg383Gly	missense_variant	Exon 2 of 5	2	NM_030786.3	ENSP00000386439.3
SYNC	ENST00000373484.4	c.1147C>G	p.Arg383Gly	missense_variant	Exon 2 of 4	2		ENSP00000362583.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461796 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727210

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Uncertain	0.059	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	17
DANN	Benign	0.97
DEOGEN2	Benign	0.32	T;.
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.64	T;T
M_CAP	Benign	0.077	D
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-0.60	T
MutationAssessor	Benign	0.34	N;N
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-2.3	N;N
REVEL	Benign	0.24
Sift	Uncertain	0.020	D;D
Sift4G	Uncertain	0.056	T;T
Polyphen		0.55	P;P
Vest4		0.19
MutPred		0.36		Loss of MoRF binding (P = 0.0109);Loss of MoRF binding (P = 0.0109);
MVP		0.37
MPC		0.68
ClinPred		0.66	D
GERP RS		0.12
Varity_R		0.16
gMVP		0.12

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: chr1-33160552;