Genetic Variant NM_007247.6:c.119C>G (chr17-37596344-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_007247.6(SYNRG):c.119C>G(p.Ala40Gly) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 1,612,542 control chromosomes in the GnomAD database, including 29,075 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.18 ( 2686 hom., cov: 33)

Exomes 𝑓: 0.19 ( 26389 hom. )

Consequence

SYNRG
NM_007247.6 missense, splice_region

Scores

Splicing: ADA: 0.003344

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.97

Publications

21 publications found

Variant links:

Genes affected

SYNRG (HGNC:557): (synergin gamma) This gene encodes a protein that interacts with the gamma subunit of AP1 clathrin-adaptor complex. The AP1 complex is located at the trans-Golgi network and associates specific proteins with clathrin-coated vesicles. This encoded protein may act to connect the AP1 complex to other proteins. Alternatively spliced transcript variants that encode different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

SYNRG links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0013802052).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNRG	NM_007247.6 link	c.119C>G	p.Ala40Gly	missense_variant, splice_region_variant	Exon 3 of 22	ENST00000612223.5	NP_009178.3	Q9UMZ2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYNRG	ENST00000612223.5 link	c.119C>G	p.Ala40Gly	missense_variant, splice_region_variant	Exon 3 of 22	1	NM_007247.6	ENSP00000483453.1		Q9UMZ2-1

Frequencies

GnomAD3 genomes

AF:

0.182

AC:

27643

AN:

152064

Hom.:

2675

Cov.:

show subpopulations

Gnomad AFR

AF:

0.138

Gnomad AMI

AF:

0.204

Gnomad AMR

AF:

0.292

Gnomad ASJ

AF:

0.162

Gnomad EAS

AF:

0.226

Gnomad SAS

AF:

0.176

Gnomad FIN

AF:

0.155

Gnomad MID

AF:

0.209

Gnomad NFE

AF:

0.185

Gnomad OTH

AF:

0.209

GnomAD2 exomes

AF:

0.201

AC:

50485

AN:

250704

AF XY:

0.197

show subpopulations

Gnomad AFR exome

AF:

0.130

Gnomad AMR exome

AF:

0.354

Gnomad ASJ exome

AF:

0.168

Gnomad EAS exome

AF:

0.233

Gnomad FIN exome

AF:

0.155

Gnomad NFE exome

AF:

0.178

Gnomad OTH exome

AF:

0.183

GnomAD4 exome

AF:

0.185

AC:

270299

AN:

1460360

Hom.:

26389

Cov.:

AF XY:

0.184

AC XY:

133838

AN XY:

726548

show subpopulations

African (AFR)

AF:

0.131

AC:

4364

AN:

33426

American (AMR)

AF:

0.344

AC:

15345

AN:

44544

Ashkenazi Jewish (ASJ)

AF:

0.170

AC:

4429

AN:

26094

East Asian (EAS)

AF:

0.214

AC:

8486

AN:

39674

South Asian (SAS)

AF:

0.183

AC:

15788

AN:

86178

European-Finnish (FIN)

AF:

0.152

AC:

8101

AN:

53288

Middle Eastern (MID)

AF:

0.207

AC:

1195

AN:

5766

European-Non Finnish (NFE)

AF:

0.181

AC:

201221

AN:

1111042

Other (OTH)

AF:

0.188

AC:

11370

AN:

60348

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

9932

19864

29797

39729

49661

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7190

14380

21570

28760

35950

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.182

AC:

27661

AN:

152182

Hom.:

2686

Cov.:

AF XY:

0.182

AC XY:

13566

AN XY:

74412

show subpopulations

African (AFR)

AF:

0.137

AC:

5705

AN:

41532

American (AMR)

AF:

0.292

AC:

4470

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.162

AC:

561

AN:

3472

East Asian (EAS)

AF:

0.225

AC:

1166

AN:

5176

South Asian (SAS)

AF:

0.175

AC:

844

AN:

4822

European-Finnish (FIN)

AF:

0.155

AC:

1640

AN:

10572

Middle Eastern (MID)

AF:

0.214

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.185

AC:

12582

AN:

68006

Other (OTH)

AF:

0.211

AC:

444

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1147

2293

3440

4586

5733

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

300

600

900

1200

1500

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.183

Hom.:

886

Bravo

AF:

0.193

TwinsUK

AF:

0.185

AC:

687

ALSPAC

AF:

0.181

AC:

697

ESP6500AA

AF:

0.128

AC:

564

ESP6500EA

AF:

0.185

AC:

1587

ExAC

AF:

0.194

AC:

23502

Asia WGS

AF:

0.191

AC:

663

AN:

3478

EpiCase

AF:

0.194

EpiControl

AF:

0.180

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0099

T;.;.;.;.

Eigen

Benign

-0.19

Eigen_PC

Benign

0.0044

FATHMM_MKL

Uncertain

0.96

M_CAP

Benign

0.0045

MetaRNN

Benign

0.0014

T;T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.34

N;N;N;N;N

PhyloP100

2.0

PrimateAI

Uncertain

0.53

Sift4G

Benign

0.39

T;T;T;T;T

Polyphen

0.0010

B;B;.;.;.

Vest4

0.12

ClinPred

0.0073

GERP RS

3.7

Varity_R

0.096

gMVP

0.084

Mutation Taster

=25/75

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0033

dbscSNV1_RF

Benign

0.13

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over