chrX-47619369-G-T

Position:

chrX-47619369-G-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_006950.3(SYN1):c.360C>A(p.Asp120Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00001 in 1,196,930 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000045 ( 0 hom., 2 hem., cov: 22)

Exomes 𝑓: 0.0000065 ( 0 hom. 2 hem. )

Consequence

SYN1
NM_006950.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.422

Variant links:

Genes affected

SYN1 (HGNC:11494): (synapsin I) This gene is a member of the synapsin gene family. Synapsins encode neuronal phosphoproteins which associate with the cytoplasmic surface of synaptic vesicles. Family members are characterized by common protein domains, and they are implicated in synaptogenesis and the modulation of neurotransmitter release, suggesting a potential role in several neuropsychiatric diseases. This member of the synapsin family plays a role in regulation of axonogenesis and synaptogenesis. The protein encoded serves as a substrate for several different protein kinases and phosphorylation may function in the regulation of this protein in the nerve terminal. Mutations in this gene may be associated with X-linked disorders with primary neuronal degeneration such as Rett syndrome. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

SYN1 links:

ENSG00000283743 (HGNC:):

ENSG00000283743 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP6

Variant X-47619369-G-T is Benign according to our data. Variant chrX-47619369-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 465097.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYN1	NM_006950.3 linkuse as main transcript	c.360C>A	p.Asp120Glu	missense_variant	1/13	ENST00000295987.13	NP_008881.2	P17600-1
SYN1	NM_133499.2 linkuse as main transcript	c.360C>A	p.Asp120Glu	missense_variant	1/13		NP_598006.1	P17600-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SYN1	ENST00000295987.13 linkuse as main transcript	c.360C>A	p.Asp120Glu	missense_variant	1/13	2	NM_006950.3	ENSP00000295987.7	P17600-1
SYN1	ENST00000340666.5 linkuse as main transcript	c.360C>A	p.Asp120Glu	missense_variant	1/13	1		ENSP00000343206.4	P17600-2
SYN1	ENST00000639776.1 linkuse as main transcript	c.18C>A	p.Asp6Glu	missense_variant	1/6	3		ENSP00000492521.1	A0A1W2PS00
ENSG00000283743	ENST00000638776.2 linkuse as main transcript	n.2833+3721C>A		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0000445

AC:

AN:

112301

Hom.:

Cov.:

AF XY:

0.0000581

AC XY:

AN XY:

34453

show subpopulations

Gnomad AFR

AF:

0.000129

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000927

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:

0.00

GnomAD3 exomes

AF:

0.0000326

AC:

AN:

153289

Hom.:

AF XY:

0.0000185

AC XY:

AN XY:

53915

show subpopulations

Gnomad AFR exome

AF:

0.000303

Gnomad AMR exome

AF:

0.0000761

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:

0.00

GnomAD4 exome

AF:

0.00000645

AC:

AN:

1084629

Hom.:

Cov.:

AF XY:

0.00000560

AC XY:

AN XY:

357117

show subpopulations

Gnomad4 AFR exome

AF:

0.000114

Gnomad4 AMR exome

AF:

0.0000574

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:

0.0000438

GnomAD4 genome

AF:

0.0000445

AC:

AN:

112301

Hom.:

Cov.:

AF XY:

0.0000581

AC XY:

AN XY:

34453

show subpopulations

Gnomad4 AFR

AF:

0.000129

Gnomad4 AMR

AF:

0.0000927

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:

0.00

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.0000907

ESP6500AA

AF:

0.000297

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00000853

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Epilepsy, X-linked 1, with variable learning disabilities and behavior disorders

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Oct 13, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.94

BayesDel_addAF

Benign

-0.039

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Pathogenic

0.82

D;.

FATHMM_MKL

Benign

0.41

LIST_S2

Uncertain

0.92

D;D

M_CAP

Pathogenic

0.63

MetaRNN

Uncertain

0.74

D;D

MetaSVM

Benign

-0.62

MutationAssessor

Uncertain

2.0

M;M

PrimateAI

Pathogenic

0.85

PROVEAN

Uncertain

-3.2

D;D

REVEL

Uncertain

0.36

Sift

Uncertain

0.0020

D;D

Sift4G

Uncertain

0.0040

D;D

Polyphen

0.92

P;D

Vest4

0.67

MutPred

0.92

Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);

MVP

0.71

MPC

1.5

ClinPred

0.40

GERP RS

-1.1

Varity_R

0.71

gMVP

0.77

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over