rs143654475

Variant names:

• chr5-1060348-C-A
• rs143654475
• NM_006598.3:c.2843G>T

Your query was ambiguous. Multiple possible variants found:

• chr5-1060348-C-A
• chr5-1060348-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_006598.3(SLC12A7):​c.2843G>T​(p.Arg948Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R948Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 35)
• Consequence: SLC12A7 NM_006598.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.06

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.76

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC12A7	NM_006598.3	c.2843G>T	p.Arg948Leu	missense_variant	Exon 21 of 24	ENST00000264930.10	NP_006589.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC12A7	ENST00000264930.10	c.2843G>T	p.Arg948Leu	missense_variant	Exon 21 of 24	1	NM_006598.3	ENSP00000264930.5
SLC12A7	ENST00000634447.1	c.2543G>T	p.Arg848Leu	missense_variant	Exon 19 of 23	5		ENSP00000489285.1
SLC12A7	ENST00000513223.2	c.938G>T	p.Arg313Leu	missense_variant	Exon 7 of 8	5		ENSP00000428854.2
SLC12A7	ENST00000514994.1	n.143G>T		non_coding_transcript_exon_variant	Exon 2 of 3	3

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 35

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.66	D
Eigen	Benign	0.076
Eigen_PC	Benign	0.080
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.069	D
MetaRNN	Pathogenic	0.76	D
MetaSVM	Benign	-0.81	T
MutationAssessor	Uncertain	2.8	M
PrimateAI	Uncertain	0.68	T
PROVEAN	Uncertain	-4.2	D
REVEL	Uncertain	0.29
Sift	Benign	0.097	T
Sift4G	Benign	0.26	T
Polyphen		0.35	B
Vest4		0.78
MutPred		0.46		Loss of methylation at K943 (P = 0.0359);
MVP		0.59
MPC		1.0
ClinPred		0.99	D
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.41
gMVP		0.55

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

Other links and lift over

dbSNP: rs143654475; hg19: chr5-1060463;