20-46051869-T-G

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_020708.5(SLC12A5):ā€‹c.2376T>Gā€‹(p.Ile792Met) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: š‘“ 0.0 ( 0 hom., cov: 28)
Exomes š‘“: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

SLC12A5
NM_020708.5 missense, splice_region

Scores

9
10
Splicing: ADA: 0.0001052
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.12
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.37809098).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC12A5NM_020708.5 linkc.2376T>G p.Ile792Met missense_variant, splice_region_variant Exon 18 of 26 ENST00000243964.7 NP_065759.1 Q9H2X9-2
SLC12A5NM_001134771.2 linkc.2445T>G p.Ile815Met missense_variant, splice_region_variant Exon 18 of 26 NP_001128243.1 Q9H2X9-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC12A5ENST00000243964.7 linkc.2376T>G p.Ile792Met missense_variant, splice_region_variant Exon 18 of 26 1 NM_020708.5 ENSP00000243964.4 Q9H2X9-2

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
0
AN:
115374
Hom.:
0
Cov.:
28
FAILED QC
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1092694
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
541454
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
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:
0.00
GnomAD4 genome
Data not reliable, filtered out with message: AC0;AS_VQSR
AF:
0.00
AC:
0
AN:
115374
Hom.:
0
Cov.:
28
AF XY:
0.00
AC XY:
0
AN XY:
52758
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.31
BayesDel_addAF
Uncertain
0.055
T
BayesDel_noAF
Benign
-0.16
CADD
Benign
3.7
DANN
Uncertain
0.98
DEOGEN2
Benign
0.39
T;.
Eigen
Benign
-0.78
Eigen_PC
Benign
-0.84
FATHMM_MKL
Benign
0.23
N
LIST_S2
Uncertain
0.88
D;D
M_CAP
Uncertain
0.17
D
MetaRNN
Benign
0.38
T;T
MetaSVM
Uncertain
0.072
D
MutationAssessor
Uncertain
2.3
M;.
PrimateAI
Uncertain
0.71
T
PROVEAN
Benign
-1.8
N;N
REVEL
Uncertain
0.44
Sift
Benign
0.030
D;D
Sift4G
Uncertain
0.050
T;T
Polyphen
0.21
B;P
Vest4
0.58
MutPred
0.50
Gain of MoRF binding (P = 0.0778);.;
MVP
0.81
MPC
1.9
ClinPred
0.51
D
GERP RS
-2.1
Varity_R
0.42
gMVP
0.93

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.00011
dbscSNV1_RF
Benign
0.062
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: rs201525976; hg19: chr20-44680508; API