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GeneBe

rs35981087

chr20-46052982-C-T

Variant summary

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

The NM_020708.5(SLC12A5):c.2403C>T(p.Gly801=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000725 in 1,613,432 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0041 ( 3 hom., cov: 33)
Exomes 𝑓: 0.00038 ( 5 hom. )

Consequence

SLC12A5
NM_020708.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.440
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 -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=-0.53).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 20-46052982-C-T is Benign according to our data. Variant chr20-46052982-C-T is described in ClinVar as [Benign]. Clinvar id is 475650.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=-0.44 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00407 (619/152234) while in subpopulation AFR AF= 0.0142 (592/41552). AF 95% confidence interval is 0.0133. There are 3 homozygotes in gnomad4. There are 283 alleles in male gnomad4 subpopulation. 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 Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SLC12A5NM_020708.5 linkuse as main transcriptc.2403C>T p.Gly801= synonymous_variant 19/26 ENST00000243964.7
SLC12A5NM_001134771.2 linkuse as main transcriptc.2472C>T p.Gly824= synonymous_variant 19/26

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SLC12A5ENST00000243964.7 linkuse as main transcriptc.2403C>T p.Gly801= synonymous_variant 19/261 NM_020708.5 A1Q9H2X9-2

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00405
AC:
616
AN:
152116
Hom.:
3
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0142
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00144
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.000957
GnomAD3 exomes
AF:
0.00100
AC:
252
AN:
251106
Hom.:
3
AF XY:
0.000744
AC XY:
101
AN XY:
135698
show subpopulations
Gnomad AFR exome
AF:
0.0138
Gnomad AMR exome
AF:
0.000695
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:
0.00000881
Gnomad OTH exome
AF:
0.000490
GnomAD4 exome
AF:
0.000377
AC:
551
AN:
1461198
Hom.:
5
Cov.:
31
AF XY:
0.000334
AC XY:
243
AN XY:
726784
show subpopulations
Gnomad4 AFR exome
AF:
0.0132
Gnomad4 AMR exome
AF:
0.000805
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000580
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000630
Gnomad4 OTH exome
AF:
0.00101
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00407
AC:
619
AN:
152234
Hom.:
3
Cov.:
33
AF XY:
0.00380
AC XY:
283
AN XY:
74440
show subpopulations
Gnomad4 AFR
AF:
0.0142
Gnomad4 AMR
AF:
0.00150
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.000947
Alfa
AF:
0.00197
Hom.:
1
Bravo
AF:
0.00464
Asia WGS
AF:
0.000577
AC:
2
AN:
3478

ClinVar

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

Submissions by phenotype

Developmental and epileptic encephalopathy, 34 Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJan 27, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.53
Cadd
Benign
8.4
Dann
Benign
0.60

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: rs35981087; hg19: chr20-44681621; API