Genetic Variant SYNRG:c.3517+84C>A (chr17-37538240-G-T) – 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.3517+84C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 1,010,134 control chromosomes in the GnomAD database, including 44,775 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.33 ( 8977 hom., cov: 32)

Exomes 𝑓: 0.27 ( 35798 hom. )

Consequence

SYNRG
NM_007247.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.294

Publications

17 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:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.563 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007247.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SYNRG	NM_007247.6	MANE Select	c.3517+84C>A	intron	N/A	NP_009178.3
SYNRG	NM_001405103.1		c.3820+84C>A	intron	N/A	NP_001392032.1
SYNRG	NM_198882.3		c.3283+84C>A	intron	N/A	NP_942583.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SYNRG	ENST00000612223.5	TSL:1 MANE Select	c.3517+84C>A	intron	N/A	ENSP00000483453.1
SYNRG	ENST00000622045.4	TSL:1	c.3283+84C>A	intron	N/A	ENSP00000483063.1
SYNRG	ENST00000619541.4	TSL:1	c.3280+84C>A	intron	N/A	ENSP00000477885.1

Frequencies

GnomAD3 genomes

AF:

0.327

AC:

49692

AN:

151934

Hom.:

8957

Cov.:

show subpopulations

Gnomad AFR

AF:

0.462

Gnomad AMI

AF:

0.249

Gnomad AMR

AF:

0.255

Gnomad ASJ

AF:

0.263

Gnomad EAS

AF:

0.581

Gnomad SAS

AF:

0.353

Gnomad FIN

AF:

0.324

Gnomad MID

AF:

0.220

Gnomad NFE

AF:

0.246

Gnomad OTH

AF:

0.287

GnomAD4 exome

AF:

0.275

AC:

235774

AN:

858082

Hom.:

35798

AF XY:

0.275

AC XY:

121133

AN XY:

440046

show subpopulations

African (AFR)

AF:

0.464

AC:

8955

AN:

19308

American (AMR)

AF:

0.263

AC:

6668

AN:

25360

Ashkenazi Jewish (ASJ)

AF:

0.254

AC:

4392

AN:

17308

East Asian (EAS)

AF:

0.596

AC:

20171

AN:

33866

South Asian (SAS)

AF:

0.333

AC:

18767

AN:

56318

European-Finnish (FIN)

AF:

0.324

AC:

15797

AN:

48790

Middle Eastern (MID)

AF:

0.239

AC:

671

AN:

2808

European-Non Finnish (NFE)

AF:

0.243

AC:

149296

AN:

615248

Other (OTH)

AF:

0.283

AC:

11057

AN:

39076

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

8009

16018

24028

32037

40046

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4140

8280

12420

16560

20700

<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:

0.327

AC:

49754

AN:

152052

Hom.:

8977

Cov.:

AF XY:

0.331

AC XY:

24600

AN XY:

74332

show subpopulations

African (AFR)

AF:

0.463

AC:

19190

AN:

41460

American (AMR)

AF:

0.254

AC:

3889

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.263

AC:

912

AN:

3470

East Asian (EAS)

AF:

0.580

AC:

3000

AN:

5170

South Asian (SAS)

AF:

0.353

AC:

1701

AN:

4822

European-Finnish (FIN)

AF:

0.324

AC:

3417

AN:

10550

Middle Eastern (MID)

AF:

0.216

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.246

AC:

16747

AN:

67966

Other (OTH)

AF:

0.288

AC:

608

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1628

3256

4885

6513

8141

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

498

996

1494

1992

2490

<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:

0.285

Hom.:

17028

Bravo

AF:

0.329

Asia WGS

AF:

0.443

AC:

1537

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

8.1

(source)

DANN

Benign

0.47

PhyloP100

0.29

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over