SLC12A7 p.Ser999Ser

Variant names:

• chr5-1057499-C-C
• NM_006598.3:c.

Your query was ambiguous. Multiple possible variants found:

• chr5-1057500--
• chr5-1057500-A-G
• chr5-1057500-A-T
• chr5-1057500-A-C
• chr5-1057501-GA-CT
• chr5-1057500-AGA-GCT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_006598.3(SLC12A7):​c. variant causes a exon region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC12A7 NM_006598.3 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.73
• Publications: 0 publications found

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]

SLC12A7 Gene-Disease associations (from GenCC):

• renal tubular acidosis, distal, 2, with progressive sensorineural hearing loss

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006598.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC12A7	NM_006598.3	MANE Select	c.		exon_region	Exon 22 of 24	NP_006589.2	Q9Y666-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC12A7	ENST00000264930.10	TSL:1 MANE Select	c.		exon_region	Exon 22 of 24	ENSP00000264930.5	Q9Y666-1
	SLC12A7	ENST00000634447.1	TSL:5	c.		exon_region	Exon 20 of 23	ENSP00000489285.1	A0A0U1RR18
	SLC12A7	ENST00000945163.1		c.		exon_region	Exon 23 of 26	ENSP00000615222.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 55

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.7

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr5-1057614;