Genetic Variant NM_003179.3:c.801C>T (chrX-49191578-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003179.3(SYP):c.801C>T(p.Ser267Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000414 in 1,209,006 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 0 hem., cov: 24)

Exomes 𝑓: 0.0000027 ( 0 hom. 0 hem. )

Consequence

SYP
NM_003179.3 synonymous

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.22

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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (REVEL=0.099).

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.801C>T	p.Ser267Ser	synonymous	Exon 6 of 7	NP_003170.1	P08247-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SYP	ENST00000263233.9	TSL:1 MANE Select	c.801C>T	p.Ser267Ser	synonymous	Exon 6 of 7	ENSP00000263233.4	P08247-1
SYP	ENST00000479808.5	TSL:1	c.801C>T	p.Ser267Ser	synonymous	Exon 6 of 6	ENSP00000418169.1	P08247-1
SYP	ENST00000920145.1		c.789C>T	p.Ser263Ser	synonymous	Exon 6 of 6	ENSP00000590204.1

Frequencies

GnomAD3 genomes

AF:

0.0000177

AC:

AN:

112996

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000321

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

GnomAD2 exomes

AF:

0.00000579

AC:

AN:

172767

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000370

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1096010

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

362030

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26385

American (AMR)

AF:

0.0000285

AC:

AN:

35120

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19344

East Asian (EAS)

AF:

0.00

AC:

AN:

30171

South Asian (SAS)

AF:

0.00

AC:

AN:

53959

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39351

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4098

European-Non Finnish (NFE)

AF:

0.00000119

AC:

AN:

841598

Other (OTH)

AF:

0.0000217

AC:

AN:

45984

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

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:

0.0000177

AC:

AN:

112996

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

35126

show subpopulations

African (AFR)

AF:

0.0000321

AC:

AN:

31109

American (AMR)

AF:

0.00

AC:

AN:

10823

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2655

East Asian (EAS)

AF:

0.00

AC:

AN:

3584

South Asian (SAS)

AF:

0.00

AC:

AN:

2805

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6283

Middle Eastern (MID)

AF:

0.00

AC:

AN:

239

European-Non Finnish (NFE)

AF:

0.0000188

AC:

AN:

53293

Other (OTH)

AF:

0.00

AC:

AN:

1521

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000302

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

DANN

Benign

0.94

PhyloP100

2.2

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over