Genetic Variant SYP:p.Gly227Gly (chrX-49191698-G-T) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_003179.3(SYP):c.681C>A(p.Gly227Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000538 in 1,207,444 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 23 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.000062 ( 0 hom., 2 hem., cov: 25)

Exomes 𝑓: 0.000053 ( 0 hom. 21 hem. )

Consequence

SYP
NM_003179.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.86

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: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.045).

BP6

Variant X-49191698-G-T is Benign according to our data. Variant chrX-49191698-G-T is described in ClinVar as Benign. ClinVar VariationId is 743063.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.86 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 2 XL gene

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.681C>A	p.Gly227Gly	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.681C>A	p.Gly227Gly	synonymous	Exon 6 of 7	ENSP00000263233.4	P08247-1
SYP	ENST00000479808.5	TSL:1	c.681C>A	p.Gly227Gly	synonymous	Exon 6 of 6	ENSP00000418169.1	P08247-1
SYP	ENST00000920145.1		c.669C>A	p.Gly223Gly	synonymous	Exon 6 of 6	ENSP00000590204.1

Frequencies

GnomAD3 genomes

AF:

0.0000616

AC:

AN:

113552

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000958

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:

0.0000749

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000618

AC:

AN:

161699

AF XY:

0.0000886

show subpopulations

Gnomad AFR exome

AF:

0.000195

Gnomad AMR exome

AF:

0.0000748

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000530

AC:

AN:

1093892

Hom.:

Cov.:

AF XY:

0.0000583

AC XY:

AN XY:

360438

show subpopulations

African (AFR)

AF:

0.000190

AC:

AN:

26323

American (AMR)

AF:

0.0000857

AC:

AN:

35009

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19291

East Asian (EAS)

AF:

0.00

AC:

AN:

30100

South Asian (SAS)

AF:

0.00

AC:

AN:

53566

European-Finnish (FIN)

AF:

0.000102

AC:

AN:

39218

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4074

European-Non Finnish (NFE)

AF:

0.0000500

AC:

AN:

840402

Other (OTH)

AF:

0.0000871

AC:

AN:

45909

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.0000616

AC:

AN:

113552

Hom.:

Cov.:

AF XY:

0.0000561

AC XY:

AN XY:

35672

show subpopulations

African (AFR)

AF:

0.0000958

AC:

AN:

31323

American (AMR)

AF:

0.00

AC:

AN:

10890

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2659

East Asian (EAS)

AF:

0.00

AC:

AN:

3615

South Asian (SAS)

AF:

0.00

AC:

AN:

2833

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6372

Middle Eastern (MID)

AF:

0.00

AC:

AN:

240

European-Non Finnish (NFE)

AF:

0.0000749

AC:

AN:

53401

Other (OTH)

AF:

0.00

AC:

AN:

1532

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.535

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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

Alfa

AF:

0.000217

Hom.:

Bravo

AF:

0.0000529

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Benign

0.90

PhyloP100

1.9

Mutation Taster

=87/13

polymorphism

(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

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over