Variant 1-32695311-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_030786.3(SYNC):c.787C>T(p.Arg263Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00468 in 1,551,630 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0027 ( 2 hom., cov: 28)

Exomes 𝑓: 0.0049 ( 40 hom. )

Consequence

SYNC
NM_030786.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.61

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 Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0066640675).

BP6

Variant 1-32695311-G-A is Benign according to our data. Variant chr1-32695311-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3770462.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNC	NM_030786.3 link	c.787C>T	p.Arg263Cys	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.787C>T	p.Arg263Cys	missense_variant	Exon 2 of 5	2	NM_030786.3	ENSP00000386439.3		Q9H7C4-1
SYNC	ENST00000373484.4 link	c.787C>T	p.Arg263Cys	missense_variant	Exon 2 of 4	2		ENSP00000362583.3		Q9H7C4-2

Frequencies

GnomAD3 genomes

AF:

0.00265

AC:

403

AN:

151840

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000774

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00158

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00561

Gnomad FIN

AF:

0.00161

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00426

Gnomad OTH

AF:

0.00480

GnomAD3 exomes

AF:

0.00362

AC:

571

AN:

157578

Hom.:

AF XY:

0.00402

AC XY:

335

AN XY:

83308

show subpopulations

Gnomad AFR exome

AF:

0.000748

Gnomad AMR exome

AF:

0.00174

Gnomad ASJ exome

AF:

0.000589

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00711

Gnomad FIN exome

AF:

0.00112

Gnomad NFE exome

AF:

0.00531

Gnomad OTH exome

AF:

0.00247

GnomAD4 exome

AF:

0.00490

AC:

6859

AN:

1399672

Hom.:

Cov.:

AF XY:

0.00509

AC XY:

3516

AN XY:

690346

show subpopulations

Gnomad4 AFR exome

AF:

0.000728

Gnomad4 AMR exome

AF:

0.00162

Gnomad4 ASJ exome

AF:

0.000953

Gnomad4 EAS exome

AF:

0.0000280

Gnomad4 SAS exome

AF:

0.00762

Gnomad4 FIN exome

AF:

0.00120

Gnomad4 NFE exome

AF:

0.00539

Gnomad4 OTH exome

AF:

0.00442

GnomAD4 genome

AF:

0.00265

AC:

403

AN:

151958

Hom.:

Cov.:

AF XY:

0.00271

AC XY:

201

AN XY:

74248

show subpopulations

Gnomad4 AFR

AF:

0.000772

Gnomad4 AMR

AF:

0.00158

Gnomad4 ASJ

AF:

0.000864

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00561

Gnomad4 FIN

AF:

0.00161

Gnomad4 NFE

AF:

0.00426

Gnomad4 OTH

AF:

0.00475

Alfa

AF:

0.00406

Hom.:

Bravo

AF:

0.00262

TwinsUK

AF:

0.00647

AC:

ALSPAC

AF:

0.00389

AC:

ESP6500AA

AF:

0.000723

AC:

ESP6500EA

AF:

0.00283

AC:

ExAC

AF:

0.00269

AC:

131

Asia WGS

AF:

0.00318

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

SYNC: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Uncertain

-0.050

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.45

T;.

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.89

D;D

M_CAP

Uncertain

0.088

MetaRNN

Benign

0.0067

T;T

MetaSVM

Uncertain

0.26

MutationAssessor

Benign

0.55

N;N

PrimateAI

Benign

0.33

PROVEAN

Uncertain

-3.4

D;D

REVEL

Uncertain

0.60

Sift

Uncertain

0.013

D;D

Sift4G

Uncertain

0.0080

D;D

Polyphen

1.0

D;D

Vest4

0.54

MVP

0.57

MPC

1.2

ClinPred

0.022

GERP RS

4.5

Varity_R

0.27

gMVP

0.37

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