1-32694954-C-A

Variant names:

• chr1-32694954-C-A
• rs749835435
• NM_030786.3:c.1144G>T

Variant summary

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

The NM_030786.3(SYNC):​c.1144G>T​(p.Ala382Ser) 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. A382T) 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: 1.75
• 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=0.3758977).

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.1144G>T	p.Ala382Ser	missense	Exon 2 of 5	NP_110413.3	Q9H7C4-1
	SYNC	NM_001161708.2		c.1144G>T	p.Ala382Ser	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.1144G>T	p.Ala382Ser	missense	Exon 2 of 5	ENSP00000386439.3	Q9H7C4-1
	SYNC	ENST00000947461.1		c.1219G>T	p.Ala407Ser	missense	Exon 3 of 6	ENSP00000617520.1
	SYNC	ENST00000854990.1		c.1144G>T	p.Ala382Ser	missense	Exon 2 of 5	ENSP00000525049.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.089	D
BayesDel_noAF	Benign	-0.11
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.31	T
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.18
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.079	D
MetaRNN	Benign	0.38	T
MetaSVM	Uncertain	-0.17	T
MutationAssessor	Benign	0.34	N
PhyloP100		1.7
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.5	N
REVEL	Uncertain	0.31
Sift	Benign	0.054	T
Sift4G	Benign	0.36	T
Polyphen		1.0	D
Vest4		0.25
MutPred		0.29		Gain of phosphorylation at A382 (P = 0.0471)
MVP		0.72
MPC		0.95
ClinPred		0.83	D
GERP RS		3.1
Varity_R		0.24
gMVP		0.18
Mutation Taster		=87/13	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: rs749835435; hg19: chr1-33160555;