Genetic Variant SYP:c.*1T>C (chrX-49191436-A-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_003179.3(SYP):c.*1T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000413 in 1,209,341 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 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 0.0000089 ( 0 hom., 1 hem., cov: 24)

Exomes 𝑓: 0.0000036 ( 0 hom. 1 hem. )

Consequence

SYP
NM_003179.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.288

Publications

0 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, STRONG, LIMITED Submitted by: Illumina, PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
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: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.4).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003179.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYP	NM_003179.3	MANE Select	c.*1T>C		3_prime_UTR	Exon 6 of 7	NP_003170.1	P08247-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SYP	ENST00000263233.9	TSL:1 MANE Select	c.*1T>C	3_prime_UTR	Exon 6 of 7	ENSP00000263233.4	P08247-1
SYP	ENST00000479808.5	TSL:1	c.*1T>C	3_prime_UTR	Exon 6 of 6	ENSP00000418169.1	P08247-1
SYP	ENST00000920145.1		c.*1T>C	3_prime_UTR	Exon 6 of 6	ENSP00000590204.1

Frequencies

GnomAD3 genomes

AF:

0.00000890

AC:

AN:

112331

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000365

AC:

AN:

1097010

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

362594

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26372

American (AMR)

AF:

0.00

AC:

AN:

35146

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19363

East Asian (EAS)

AF:

0.0000331

AC:

AN:

30168

South Asian (SAS)

AF:

0.00

AC:

AN:

53935

European-Finnish (FIN)

AF:

0.0000498

AC:

AN:

40189

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4120

European-Non Finnish (NFE)

AF:

0.00000119

AC:

AN:

841682

Other (OTH)

AF:

0.00

AC:

AN:

46035

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.00000890

AC:

AN:

112331

Hom.:

Cov.:

AF XY:

0.0000290

AC XY:

AN XY:

34517

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30943

American (AMR)

AF:

0.00

AC:

AN:

10687

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2649

East Asian (EAS)

AF:

0.00

AC:

AN:

3588

South Asian (SAS)

AF:

0.00

AC:

AN:

2767

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6125

Middle Eastern (MID)

AF:

0.00

AC:

AN:

238

European-Non Finnish (NFE)

AF:

0.0000188

AC:

AN:

53138

Other (OTH)

AF:

0.00

AC:

AN:

1511

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Benign

0.63

PhyloP100

0.29

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

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over