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rs3746519

chr20-46037307-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_020708.5(SLC12A5):c.534T>C(p.Gly178=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0276 in 1,612,408 control chromosomes in the GnomAD database, including 1,188 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.029 ( 170 hom., cov: 31)
Exomes 𝑓: 0.027 ( 1018 hom. )

Consequence

SLC12A5
NM_020708.5 synonymous

Scores

2

Clinical Significance

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

Conservation

PhyloP100: -0.419
Variant links:
Genes affected
SLC12A5 (HGNC:13818): (solute carrier family 12 member 5) K-Cl cotransporters are proteins that lower intracellular chloride concentrations below the electrochemical equilibrium potential. The protein encoded by this gene is an integral membrane K-Cl cotransporter that can function in either a net efflux or influx pathway, depending on the chemical concentration gradients of potassium and chloride. The encoded protein can act as a homomultimer, or as a heteromultimer with other K-Cl cotransporters, to maintain chloride homeostasis in neurons. Alternative splicing results in two transcript variants encoding different isoforms. [provided by RefSeq, Sep 2008]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 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=-0.54).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 20-46037307-T-C is Benign according to our data. Variant chr20-46037307-T-C is described in ClinVar as [Benign]. Clinvar id is 475658.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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=-0.419 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SLC12A5NM_020708.5 linkuse as main transcriptc.534T>C p.Gly178= synonymous_variant 6/26 ENST00000243964.7
SLC12A5NM_001134771.2 linkuse as main transcriptc.603T>C p.Gly201= synonymous_variant 6/26

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SLC12A5ENST00000243964.7 linkuse as main transcriptc.534T>C p.Gly178= synonymous_variant 6/261 NM_020708.5 A1Q9H2X9-2

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0291
AC:
4412
AN:
151854
Hom.:
167
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00804
Gnomad AMI
AF:
0.0395
Gnomad AMR
AF:
0.118
Gnomad ASJ
AF:
0.0539
Gnomad EAS
AF:
0.0276
Gnomad SAS
AF:
0.0273
Gnomad FIN
AF:
0.0184
Gnomad MID
AF:
0.00633
Gnomad NFE
AF:
0.0223
Gnomad OTH
AF:
0.0344
GnomAD3 exomes
AF:
0.0411
AC:
10297
AN:
250386
Hom.:
527
AF XY:
0.0370
AC XY:
5014
AN XY:
135374
show subpopulations
Gnomad AFR exome
AF:
0.00567
Gnomad AMR exome
AF:
0.150
Gnomad ASJ exome
AF:
0.0513
Gnomad EAS exome
AF:
0.0289
Gnomad SAS exome
AF:
0.0300
Gnomad FIN exome
AF:
0.0215
Gnomad NFE exome
AF:
0.0212
Gnomad OTH exome
AF:
0.0387
GnomAD4 exome
AF:
0.0274
AC:
40065
AN:
1460436
Hom.:
1018
Cov.:
31
AF XY:
0.0271
AC XY:
19710
AN XY:
726598
show subpopulations
Gnomad4 AFR exome
AF:
0.00511
Gnomad4 AMR exome
AF:
0.149
Gnomad4 ASJ exome
AF:
0.0529
Gnomad4 EAS exome
AF:
0.0346
Gnomad4 SAS exome
AF:
0.0298
Gnomad4 FIN exome
AF:
0.0192
Gnomad4 NFE exome
AF:
0.0225
Gnomad4 OTH exome
AF:
0.0296
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0291
AC:
4417
AN:
151972
Hom.:
170
Cov.:
31
AF XY:
0.0309
AC XY:
2297
AN XY:
74258
show subpopulations
Gnomad4 AFR
AF:
0.00801
Gnomad4 AMR
AF:
0.118
Gnomad4 ASJ
AF:
0.0539
Gnomad4 EAS
AF:
0.0275
Gnomad4 SAS
AF:
0.0273
Gnomad4 FIN
AF:
0.0184
Gnomad4 NFE
AF:
0.0223
Gnomad4 OTH
AF:
0.0350
Alfa
AF:
0.0231
Hom.:
36
Bravo
AF:
0.0348
Asia WGS
AF:
0.0270
AC:
94
AN:
3478
EpiCase
AF:
0.0229
EpiControl
AF:
0.0244

ClinVar

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

Submissions by phenotype

Developmental and epileptic encephalopathy, 34 Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeFeb 01, 2024- -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxNov 12, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.54
Cadd
Benign
7.3
Dann
Benign
0.74

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

LitVar

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

Other links and lift over

dbSNP: rs3746519; hg19: chr20-44665946; API