5-1057500-AGA-GCT

Variant names:

• chr5-1057500-AGA-GCT
• NM_006598.3:c.2995_2997delTCTinsAGC
• SLC12A7 p.1000

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP7

The NM_006598.3(SLC12A7):​c.2995_2997delTCTinsAGC​(p.1000) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S999S) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC12A7 NM_006598.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.67
• 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: Likely_benign. The variant received -1 ACMG points.

• BP7: Synonymous conserved (PhyloP=1.67 with no splicing effect.

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.2995_2997delTCTinsAGC	p.1000	synonymous	N/A	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.2995_2997delTCTinsAGC	p.1000	synonymous	N/A	ENSP00000264930.5	Q9Y666-1
	SLC12A7	ENST00000634447.1	TSL:5	c.2695_2697delTCTinsAGC	p.900	synonymous	N/A	ENSP00000489285.1	A0A0U1RR18
	SLC12A7	ENST00000945163.1		c.3097_3099delTCTinsAGC	p.1034	synonymous	N/A	ENSP00000615222.1

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

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: chr5-1057615;