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GeneBe

X-49191674-C-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_003179.3(SYP):c.705G>C(p.Ala235=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000324 in 1,205,026 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 12 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00019 ( 0 hom., 8 hem., cov: 25)
Exomes 𝑓: 0.000016 ( 0 hom. 4 hem. )

Consequence

SYP
NM_003179.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.983
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.61).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant X-49191674-C-G is Benign according to our data. Variant chrX-49191674-C-G is described in ClinVar as [Benign]. Clinvar id is 752111.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.983 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000195 (22/112953) while in subpopulation AMR AF= 0.00166 (18/10843). AF 95% confidence interval is 0.00107. There are 0 homozygotes in gnomad4. There are 8 alleles in male gnomad4 subpopulation. Median coverage is 25. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Hemizygotes in GnomAd at 8 XL gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SYPNM_003179.3 linkuse as main transcriptc.705G>C p.Ala235= synonymous_variant 6/7 ENST00000263233.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SYPENST00000263233.9 linkuse as main transcriptc.705G>C p.Ala235= synonymous_variant 6/71 NM_003179.3 P1P08247-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000195
AC:
22
AN:
112901
Hom.:
0
Cov.:
25
AF XY:
0.000228
AC XY:
8
AN XY:
35087
show subpopulations
Gnomad AFR
AF:
0.0000322
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00166
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:
0.00
Gnomad OTH
AF:
0.00197
GnomAD3 exomes
AF:
0.0000625
AC:
10
AN:
159891
Hom.:
0
AF XY:
0.0000545
AC XY:
3
AN XY:
55069
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000341
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000248
GnomAD4 exome
AF:
0.0000156
AC:
17
AN:
1092073
Hom.:
0
Cov.:
31
AF XY:
0.0000111
AC XY:
4
AN XY:
358915
show subpopulations
Gnomad4 AFR exome
AF:
0.0000381
Gnomad4 AMR exome
AF:
0.000345
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000874
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000195
AC:
22
AN:
112953
Hom.:
0
Cov.:
25
AF XY:
0.000228
AC XY:
8
AN XY:
35149
show subpopulations
Gnomad4 AFR
AF:
0.0000321
Gnomad4 AMR
AF:
0.00166
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00195
Bravo
AF:
0.000499

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJul 20, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.61
Cadd
Benign
10
Dann
Benign
0.78

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs782650560; hg19: chrX-49048131; API