1-32695558-C-G

Variant names:

• chr1-32695558-C-G
• rs138479784
• NM_030786.3:c.540G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_030786.3(SYNC):​c.540G>C​(p.Gln180His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,399,508 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. Q180Q) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 28)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SYNC NM_030786.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.85
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30266505).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030786.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNC	NM_030786.3	MANE Select	c.540G>C	p.Gln180His	missense	Exon 2 of 5	NP_110413.3	Q9H7C4-1
	SYNC	NM_001161708.2		c.540G>C	p.Gln180His	missense	Exon 2 of 4	NP_001155180.2	Q9H7C4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNC	ENST00000409190.8	TSL:2 MANE Select	c.540G>C	p.Gln180His	missense	Exon 2 of 5	ENSP00000386439.3	Q9H7C4-1
	SYNC	ENST00000947461.1		c.615G>C	p.Gln205His	missense	Exon 3 of 6	ENSP00000617520.1
	SYNC	ENST00000854990.1		c.540G>C	p.Gln180His	missense	Exon 2 of 5	ENSP00000525049.1

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1399508 Hom.: 0 Cov.: 98 AF XY: 0.00000145 AC XY: 1 AN XY: 690260

African (AFR) AF: 0.00 AC: 0 AN: 31598

American (AMR) AF: 0.00 AC: 0 AN: 35704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25182

East Asian (EAS) AF: 0.00 AC: 0 AN: 35738

South Asian (SAS) AF: 0.00 AC: 0 AN: 79236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49324

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 0.00000185 AC: 2 AN: 1078996

Other (OTH) AF: 0.00 AC: 0 AN: 58032

GnomAD4 genome Cov.: 28

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Uncertain	0.067	T
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.44	T
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.0088	T
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.34	N
PhyloP100		1.9
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.16
Sift	Uncertain	0.018	D
Sift4G	Uncertain	0.0060	D
Polyphen		1.0	D
Vest4		0.26
MutPred		0.15		Loss of disorder (P = 0.1092)
MVP		0.53
MPC		0.69
ClinPred		0.91	D
GERP RS		3.6
Varity_R		0.37
gMVP		0.19
Mutation Taster		=50/50

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

Other links and lift over

dbSNP: rs138479784; hg19: chr1-33161159;