rs751771078

Variant names:

• chr1-32694918-C-T
• rs751771078
• NM_030786.3:c.1180G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_030786.3(SYNC):​c.1180G>A​(p.Asp394Asn) 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. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: SYNC NM_030786.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.29
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16330597).

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.1180G>A	p.Asp394Asn	missense	Exon 2 of 5	NP_110413.3	Q9H7C4-1
	SYNC	NM_001161708.2		c.1180G>A	p.Asp394Asn	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.1180G>A	p.Asp394Asn	missense	Exon 2 of 5	ENSP00000386439.3	Q9H7C4-1
	SYNC	ENST00000947461.1		c.1255G>A	p.Asp419Asn	missense	Exon 3 of 6	ENSP00000617520.1
	SYNC	ENST00000854990.1		c.1180G>A	p.Asp394Asn	missense	Exon 2 of 5	ENSP00000525049.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250744 AF XY: 0.00000738

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000547

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	23
DANN	Benign	0.96
DEOGEN2	Benign	0.17	T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.31
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.067	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.49	T
MutationAssessor	Benign	0.34	N
PhyloP100		2.3
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.18
Sift	Benign	0.045	D
Sift4G	Uncertain	0.016	D
Polyphen		0.10	B
Vest4		0.17
MutPred		0.32		Gain of MoRF binding (P = 0.0667)
MVP		0.63
MPC		0.43
ClinPred		0.37	T
GERP RS		2.4
Varity_R		0.20
gMVP		0.12
Mutation Taster		=78/22	polymorphism

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: rs751771078; hg19: chr1-33160519;