rs777523751

Variant names:

• chr1-32695223-C-A
• rs777523751
• NM_030786.3:c.875G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-32695223-C-A
• chr1-32695223-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_030786.3(SYNC):​c.875G>T​(p.Arg292Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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. R292Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: SYNC NM_030786.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.259

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35044897).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNC	NM_030786.3	c.875G>T	p.Arg292Leu	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.875G>T	p.Arg292Leu	missense_variant	Exon 2 of 5	2	NM_030786.3	ENSP00000386439.3
SYNC	ENST00000373484.4	c.875G>T	p.Arg292Leu	missense_variant	Exon 2 of 4	2		ENSP00000362583.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Uncertain	0.030	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	15
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.68	D;.
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.39	N
LIST_S2	Benign	0.70	T;T
M_CAP	Uncertain	0.26	D
MetaRNN	Benign	0.35	T;T
MetaSVM	Benign	-0.40	T
MutationAssessor	Benign	0.69	N;N
PrimateAI	Benign	0.28	T
PROVEAN	Pathogenic	-4.7	D;D
REVEL	Uncertain	0.46
Sift	Uncertain	0.0030	D;D
Sift4G	Benign	0.24	T;T
Polyphen		0.85	P;P
Vest4		0.41
MutPred		0.56		Loss of MoRF binding (P = 0.0415);Loss of MoRF binding (P = 0.0415);
MVP		0.33
MPC		0.99
ClinPred		0.96	D
GERP RS		-1.0
Varity_R		0.29
gMVP		0.34

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

Other links and lift over

dbSNP: rs777523751; hg19: chr1-33160824;