Variant 1-32695086-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_030786.3(SYNC):c.1012G>A(p.Asp338Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000341 in 1,613,488 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00035 ( 6 hom. )

Consequence

SYNC
NM_030786.3 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.29

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0066973567).

BP6

Variant 1-32695086-C-T is Benign according to our data. Variant chr1-32695086-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3049054.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNC	NM_030786.3 link	c.1012G>A	p.Asp338Asn	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.1012G>A	p.Asp338Asn	missense_variant	Exon 2 of 5	2	NM_030786.3	ENSP00000386439.3		Q9H7C4-1
SYNC	ENST00000373484.4 link	c.1012G>A	p.Asp338Asn	missense_variant	Exon 2 of 4	2		ENSP00000362583.3		Q9H7C4-2

Frequencies

GnomAD3 genomes

AF:

0.000217

AC:

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00373

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000680

AC:

170

AN:

250010

Hom.:

AF XY:

0.000961

AC XY:

130

AN XY:

135298

show subpopulations

Gnomad AFR exome

AF:

0.0000620

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00119

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00457

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000133

Gnomad OTH exome

AF:

0.000327

GnomAD4 exome

AF:

0.000354

AC:

518

AN:

1461218

Hom.:

Cov.:

AF XY:

0.000469

AC XY:

341

AN XY:

726856

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000957

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00455

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000585

Gnomad4 OTH exome

AF:

0.000497

GnomAD4 genome

AF:

0.000210

AC:

AN:

152270

Hom.:

Cov.:

AF XY:

0.000201

AC XY:

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00352

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000242

Hom.:

Bravo

AF:

0.000144

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ExAC

AF:

0.000659

AC:

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000474

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SYNC-related disorder

Benign:1

Jan 12, 2023

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.48

T;.

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.088

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.85

T;T

M_CAP

Benign

0.041

MetaRNN

Benign

0.0067

T;T

MetaSVM

Benign

-0.61

MutationAssessor

Benign

0.0

N;N

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.97

N;N

REVEL

Benign

0.23

Sift

Benign

0.070

T;T

Sift4G

Benign

0.47

T;T

Polyphen

0.0

B;B

Vest4

0.12

MutPred

0.36

Gain of catalytic residue at D338 (P = 0.1788);Gain of catalytic residue at D338 (P = 0.1788);

MVP

0.55

MPC

0.31

ClinPred

0.071

GERP RS

4.4

Varity_R

0.21

gMVP

0.14

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