5-1052421-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006598.3(SLC12A7):​c.3191G>A​(p.Gly1064Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000415 in 1,612,786 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000044 ( 0 hom. )

Consequence

SLC12A7
NM_006598.3 missense

Scores

1
12
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.834
Variant links:
Genes affected
SLC12A7 (HGNC:10915): (solute carrier family 12 member 7) Enables protein kinase binding activity. Predicted to be involved in several processes, including cell volume homeostasis; inorganic ion homeostasis; and inorganic ion transmembrane transport. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.18434909).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC12A7NM_006598.3 linkc.3191G>A p.Gly1064Glu missense_variant Exon 24 of 24 ENST00000264930.10 NP_006589.2 Q9Y666-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC12A7ENST00000264930.10 linkc.3191G>A p.Gly1064Glu missense_variant Exon 24 of 24 1 NM_006598.3 ENSP00000264930.5 Q9Y666-1
SLC12A7ENST00000634447.1 linkc.2906G>A p.Gly969Glu missense_variant Exon 23 of 23 5 ENSP00000489285.1 A0A0U1RR18

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152208
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.000864
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:
0.0000764
AC:
19
AN:
248752
Hom.:
0
AF XY:
0.0000742
AC XY:
10
AN XY:
134812
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00159
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000180
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000438
AC:
64
AN:
1460578
Hom.:
0
Cov.:
31
AF XY:
0.0000385
AC XY:
28
AN XY:
726582
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00149
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000108
Gnomad4 OTH exome
AF:
0.000215
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152208
Hom.:
0
Cov.:
33
AF XY:
0.0000403
AC XY:
3
AN XY:
74362
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.000864
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:
0.000203
Hom.:
1
Bravo
AF:
0.0000378
ExAC
AF:
0.0000988
AC:
12

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
May 30, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.3191G>A (p.G1064E) alteration is located in exon 24 (coding exon 24) of the SLC12A7 gene. This alteration results from a G to A substitution at nucleotide position 3191, causing the glycine (G) at amino acid position 1064 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.41
BayesDel_addAF
Benign
-0.093
T
BayesDel_noAF
Benign
-0.31
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.77
D
Eigen
Uncertain
0.48
Eigen_PC
Uncertain
0.36
FATHMM_MKL
Benign
0.41
N
LIST_S2
Uncertain
0.96
D
M_CAP
Uncertain
0.22
D
MetaRNN
Benign
0.18
T
MetaSVM
Benign
-0.48
T
MutationAssessor
Uncertain
2.9
M
PrimateAI
Uncertain
0.79
T
PROVEAN
Pathogenic
-6.0
D
REVEL
Uncertain
0.30
Sift
Uncertain
0.0030
D
Sift4G
Uncertain
0.0060
D
Polyphen
0.97
D
Vest4
0.33
MutPred
0.37
Gain of solvent accessibility (P = 0.0837);
MVP
0.80
MPC
0.94
ClinPred
0.57
D
GERP RS
3.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.65
gMVP
0.62

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: rs766126047; hg19: chr5-1052536; API