dbSNP rs3817678: SYP:c.*569C>T (chrX-49190868-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000479808.5(SYP):c.*569C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.516 in 114,473 control chromosomes in the GnomAD database, including 12,573 homozygotes. There are 17,002 hemizygotes in GnomAD. 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 0.51 ( 12007 hom., 16351 hem., cov: 23)

Exomes 𝑓: 0.57 ( 566 hom. 651 hem. )

Consequence

SYP
ENST00000479808.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.253

Publications

5 publications found

Variant links:

Genes affected

SYP (HGNC:11506): (synaptophysin) This gene encodes an integral membrane protein of small synaptic vesicles in brain and endocrine cells. The protein also binds cholesterol and is thought to direct targeting of vesicle-associated membrane protein 2 (synaptobrevin) to intracellular compartments. Mutations in this gene are associated with an X-linked form of cognitive disability. [provided by RefSeq, Jul 2017]

SYP Gene-Disease associations (from GenCC):

intellectual disability, X-linked 96
Inheritance: XL Classification: DEFINITIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, Illumina
non-syndromic X-linked intellectual disability
Inheritance: XL Classification: MODERATE, SUPPORTIVE Submitted by: Orphanet, ClinGen

SYP 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 (BayesDel_noAF=-0.58).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.664 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYP	NM_003179.3 link	c.*4+565C>T		intron_variant	Intron 6 of 6	ENST00000263233.9	NP_003170.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYP	ENST00000263233.9 link	c.*4+565C>T		intron_variant	Intron 6 of 6	1	NM_003179.3	ENSP00000263233.4

Frequencies

GnomAD3 genomes

AF:

0.515

AC:

56662

AN:

110109

Hom.:

12013

Cov.:

show subpopulations

Gnomad AFR

AF:

0.242

Gnomad AMI

AF:

0.605

Gnomad AMR

AF:

0.426

Gnomad ASJ

AF:

0.775

Gnomad EAS

AF:

0.339

Gnomad SAS

AF:

0.621

Gnomad FIN

AF:

0.608

Gnomad MID

AF:

0.658

Gnomad NFE

AF:

0.670

Gnomad OTH

AF:

0.547

GnomAD4 exome

AF:

0.572

AC:

2465

AN:

4312

Hom.:

566

Cov.:

AF XY:

0.597

AC XY:

651

AN XY:

1090

show subpopulations

African (AFR)

AF:

0.157

AC:

AN:

American (AMR)

AF:

0.368

AC:

286

AN:

778

Ashkenazi Jewish (ASJ)

AF:

0.800

AC:

AN:

East Asian (EAS)

AF:

0.266

AC:

AN:

154

South Asian (SAS)

AF:

0.636

AC:

525

AN:

826

European-Finnish (FIN)

AF:

0.586

AC:

AN:

Middle Eastern (MID)

AF:

0.667

AC:

AN:

European-Non Finnish (NFE)

AF:

0.643

AC:

1466

AN:

2281

Other (OTH)

AF:

0.617

AC:

AN:

141

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

128

160

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

<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:

0.514

AC:

56656

AN:

110161

Hom.:

12007

Cov.:

AF XY:

0.504

AC XY:

16351

AN XY:

32463

show subpopulations

African (AFR)

AF:

0.241

AC:

7352

AN:

30448

American (AMR)

AF:

0.425

AC:

4435

AN:

10424

Ashkenazi Jewish (ASJ)

AF:

0.775

AC:

2032

AN:

2622

East Asian (EAS)

AF:

0.339

AC:

1181

AN:

3480

South Asian (SAS)

AF:

0.625

AC:

1626

AN:

2602

European-Finnish (FIN)

AF:

0.608

AC:

3468

AN:

5701

Middle Eastern (MID)

AF:

0.654

AC:

138

AN:

211

European-Non Finnish (NFE)

AF:

0.670

AC:

35198

AN:

52511

Other (OTH)

AF:

0.550

AC:

823

AN:

1496

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

837

1675

2512

3350

4187

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

520

1040

1560

2080

2600

<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:

0.581

Hom.:

5752

Bravo

AF:

0.485

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

5.4

(source)

PhyloP100

0.25

Splicing

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over