5-1060348-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006598.3(SLC12A7):​c.2843G>A​(p.Arg948Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000378 in 1,612,332 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 35)
Exomes 𝑓: 0.000038 ( 0 hom. )

Consequence

SLC12A7
NM_006598.3 missense

Scores

3
6
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.06
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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC12A7NM_006598.3 linkc.2843G>A p.Arg948Gln missense_variant Exon 21 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.2843G>A p.Arg948Gln missense_variant Exon 21 of 24 1 NM_006598.3 ENSP00000264930.5 Q9Y666-1
SLC12A7ENST00000634447.1 linkc.2543G>A p.Arg848Gln missense_variant Exon 19 of 23 5 ENSP00000489285.1 A0A0U1RR18
SLC12A7ENST00000513223.2 linkc.938G>A p.Arg313Gln missense_variant Exon 7 of 8 5 ENSP00000428854.2 H0YB78
SLC12A7ENST00000514994.1 linkn.143G>A non_coding_transcript_exon_variant Exon 2 of 3 3

Frequencies

GnomAD3 genomes
AF:
0.0000328
AC:
5
AN:
152226
Hom.:
0
Cov.:
35
show subpopulations
Gnomad AFR
AF:
0.0000241
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:
0.0000588
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000359
AC:
9
AN:
250850
Hom.:
0
AF XY:
0.0000295
AC XY:
4
AN XY:
135732
show subpopulations
Gnomad AFR exome
AF:
0.0000616
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000163
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000353
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000384
AC:
56
AN:
1459988
Hom.:
0
Cov.:
31
AF XY:
0.0000317
AC XY:
23
AN XY:
726372
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000486
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000328
AC:
5
AN:
152344
Hom.:
0
Cov.:
35
AF XY:
0.0000268
AC XY:
2
AN XY:
74502
show subpopulations
Gnomad4 AFR
AF:
0.0000241
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:
0.0000588
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000264
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000233
AC:
2
ExAC
AF:
0.0000659
AC:
8
EpiCase
AF:
0.000109
EpiControl
AF:
0.00

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Feb 16, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.2843G>A (p.R948Q) alteration is located in exon 21 (coding exon 21) of the SLC12A7 gene. This alteration results from a G to A substitution at nucleotide position 2843, causing the arginine (R) at amino acid position 948 to be replaced by a glutamine (Q). 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
Benign
0.11
BayesDel_addAF
Benign
-0.098
T
BayesDel_noAF
Benign
-0.11
CADD
Uncertain
25
DANN
Pathogenic
1.0
DEOGEN2
Uncertain
0.52
D
Eigen
Uncertain
0.36
Eigen_PC
Uncertain
0.28
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Pathogenic
0.99
D
M_CAP
Benign
0.054
D
MetaRNN
Uncertain
0.59
D
MetaSVM
Benign
-0.72
T
MutationAssessor
Uncertain
2.8
M
PrimateAI
Uncertain
0.64
T
PROVEAN
Benign
-1.9
N
REVEL
Benign
0.26
Sift
Benign
0.048
D
Sift4G
Benign
0.14
T
Polyphen
0.98
D
Vest4
0.61
MVP
0.74
MPC
0.95
ClinPred
0.35
T
GERP RS
4.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.21
gMVP
0.46

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: rs143654475; hg19: chr5-1060463; API