chr11-20601059-A-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004211.5(SLC6A5):​c.4-70A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.1 in 1,479,216 control chromosomes in the GnomAD database, including 8,076 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1025 hom., cov: 33)
Exomes 𝑓: 0.099 ( 7051 hom. )

Consequence

SLC6A5
NM_004211.5 intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.18

Publications

1 publications found
Variant links:
Genes affected
SLC6A5 (HGNC:11051): (solute carrier family 6 member 5) This gene encodes a sodium- and chloride-dependent glycine neurotransmitter transporter. This integral membrane glycoprotein is responsible for the clearance of extracellular glycine during glycine-mediated neurotransmission. This protein is found in glycinergic axons and maintains a high presynaptic pool of neurotransmitter at glycinergic synapses. Mutations in this gene cause hyperekplexia; a heterogenous neurological disorder characterized by exaggerated startle responses and neonatal apnea. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2016]
SLC6A5 Gene-Disease associations (from GenCC):
  • hyperekplexia 3
    Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
  • hereditary hyperekplexia
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP6
Variant 11-20601059-A-G is Benign according to our data. Variant chr11-20601059-A-G is described in ClinVar as Benign. ClinVar VariationId is 1297945.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC6A5NM_004211.5 linkc.4-70A>G intron_variant Intron 1 of 15 ENST00000525748.6 NP_004202.4 Q9Y345-1Q4VAM4Q4VAM6
SLC6A5NM_001318369.2 linkc.-560-70A>G intron_variant Intron 1 of 14 NP_001305298.1 Q9Y345-2Q4VAM4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC6A5ENST00000525748.6 linkc.4-70A>G intron_variant Intron 1 of 15 1 NM_004211.5 ENSP00000434364.2 Q9Y345-1
SLC6A5ENST00000298923.11 linkn.4-70A>G intron_variant Intron 1 of 14 1 ENSP00000298923.7 J3KNC4

Frequencies

GnomAD3 genomes
AF:
0.111
AC:
16849
AN:
152154
Hom.:
1023
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.164
Gnomad AMI
AF:
0.0833
Gnomad AMR
AF:
0.0875
Gnomad ASJ
AF:
0.138
Gnomad EAS
AF:
0.00693
Gnomad SAS
AF:
0.0641
Gnomad FIN
AF:
0.0511
Gnomad MID
AF:
0.117
Gnomad NFE
AF:
0.104
Gnomad OTH
AF:
0.0957
GnomAD4 exome
AF:
0.0991
AC:
131442
AN:
1326944
Hom.:
7051
AF XY:
0.0982
AC XY:
64473
AN XY:
656478
show subpopulations
African (AFR)
AF:
0.168
AC:
4916
AN:
29276
American (AMR)
AF:
0.0686
AC:
2001
AN:
29152
Ashkenazi Jewish (ASJ)
AF:
0.149
AC:
3501
AN:
23434
East Asian (EAS)
AF:
0.00215
AC:
77
AN:
35742
South Asian (SAS)
AF:
0.0595
AC:
4410
AN:
74072
European-Finnish (FIN)
AF:
0.0576
AC:
1961
AN:
34056
Middle Eastern (MID)
AF:
0.0976
AC:
534
AN:
5474
European-Non Finnish (NFE)
AF:
0.104
AC:
108314
AN:
1040042
Other (OTH)
AF:
0.103
AC:
5728
AN:
55696
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.503
Heterozygous variant carriers
0
5935
11870
17804
23739
29674
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
4046
8092
12138
16184
20230
<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:
0.111
AC:
16857
AN:
152272
Hom.:
1025
Cov.:
33
AF XY:
0.106
AC XY:
7871
AN XY:
74462
show subpopulations
African (AFR)
AF:
0.164
AC:
6796
AN:
41540
American (AMR)
AF:
0.0873
AC:
1336
AN:
15300
Ashkenazi Jewish (ASJ)
AF:
0.138
AC:
480
AN:
3472
East Asian (EAS)
AF:
0.00694
AC:
36
AN:
5186
South Asian (SAS)
AF:
0.0635
AC:
307
AN:
4834
European-Finnish (FIN)
AF:
0.0511
AC:
543
AN:
10616
Middle Eastern (MID)
AF:
0.116
AC:
34
AN:
294
European-Non Finnish (NFE)
AF:
0.104
AC:
7049
AN:
68006
Other (OTH)
AF:
0.0947
AC:
200
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.503
Heterozygous variant carriers
0
767
1533
2300
3066
3833
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
176
352
528
704
880
<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:
0.102
Hom.:
294
Bravo
AF:
0.115
Asia WGS
AF:
0.0530
AC:
189
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:not provided

- -

May 17, 2021
GeneDx
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.80
CADD
Benign
0.015
DANN
Benign
0.55
PhyloP100
-1.2
Mutation Taster
=100/0
polymorphism (auto)

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs72944437; hg19: chr11-20622605; API