Variant NM_030786.3:c.757T>C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_030786.3(SYNC):c.757T>C(p.Cys253Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000018 in 1,551,336 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 28)

Exomes 𝑓: 0.0000086 ( 0 hom. )

Consequence

SYNC
NM_030786.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.73

Variant links:

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]

SYNC links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNC	NM_030786.3 link	c.757T>C	p.Cys253Arg	missense_variant	Exon 2 of 5	ENST00000409190.8	NP_110413.3	Q9H7C4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYNC	ENST00000409190.8 link	c.757T>C	p.Cys253Arg	missense_variant	Exon 2 of 5	2	NM_030786.3	ENSP00000386439.3		Q9H7C4-1
SYNC	ENST00000373484.4 link	c.757T>C	p.Cys253Arg	missense_variant	Exon 2 of 4	2		ENSP00000362583.3		Q9H7C4-2

Frequencies

GnomAD3 genomes

AF:

0.000106

AC:

AN:

151594

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000364

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000209

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000381

AC:

AN:

157538

Hom.:

AF XY:

0.0000480

AC XY:

AN XY:

83258

show subpopulations

Gnomad AFR exome

AF:

0.000620

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000439

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000857

AC:

AN:

1399742

Hom.:

Cov.:

AF XY:

0.00000724

AC XY:

AN XY:

690380

show subpopulations

Gnomad4 AFR exome

AF:

0.000190

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000379

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000278

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.000106

AC:

AN:

151594

Hom.:

Cov.:

AF XY:

0.0000947

AC XY:

AN XY:

73954

show subpopulations

Gnomad4 AFR

AF:

0.000364

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000209

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000134

Hom.:

ExAC

AF:

0.0000523

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 18, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.757T>C (p.C253R) alteration is located in exon 2 (coding exon 2) of the SYNC gene. This alteration results from a T to C substitution at nucleotide position 757, causing the cysteine (C) at amino acid position 253 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.80

BayesDel_addAF

Uncertain

0.022

BayesDel_noAF

Pathogenic

0.16

CADD

Pathogenic

DANN

Benign

0.91

DEOGEN2

Benign

0.20

T;.

Eigen

Uncertain

0.29

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.81

T;T

M_CAP

Uncertain

0.18

MetaRNN

Uncertain

0.63

D;D

MetaSVM

Uncertain

-0.20

MutationAssessor

Benign

1.0

L;L

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-2.0

N;N

REVEL

Pathogenic

0.75

Sift

Benign

1.0

T;T

Sift4G

Benign

0.42

T;T

Polyphen

1.0

D;D

Vest4

0.86

MVP

0.56

MPC

1.4

ClinPred

0.15

GERP RS

4.5

Varity_R

0.59

gMVP

0.65

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over