20-46022179-A-C

Variant names:

• chr20-46022179-A-C
• rs6130997
• NM_001134771.2:c.121+293A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001134771.2(SLC12A5):​c.121+293A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SLC12A5 NM_001134771.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0270
• Publications: 8 publications found

Genes affected

SLC12A5 (HGNC:13818): (solute carrier family 12 member 5) K-Cl cotransporters are proteins that lower intracellular chloride concentrations below the electrochemical equilibrium potential. The protein encoded by this gene is an integral membrane K-Cl cotransporter that can function in either a net efflux or influx pathway, depending on the chemical concentration gradients of potassium and chloride. The encoded protein can act as a homomultimer, or as a heteromultimer with other K-Cl cotransporters, to maintain chloride homeostasis in neurons. Alternative splicing results in two transcript variants encoding different isoforms. [provided by RefSeq, Sep 2008]

SLC12A5-AS1 (HGNC:53143): (SLC12A5 and MMP9 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001134771.2. 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
	SLC12A5	NM_001134771.2		c.121+293A>C		intron	N/A	NP_001128243.1	Q9H2X9-1
	SLC12A5-AS1	NR_147699.1		n.-106T>G		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC12A5	ENST00000454036.6	TSL:5	c.121+293A>C		intron	N/A	ENSP00000387694.1	Q9H2X9-1
	SLC12A5	ENST00000626701.1	TSL:3	c.121+293A>C		intron	N/A	ENSP00000487372.1	A0A0D9SGD0
	SLC12A5	ENST00000413737.2	TSL:3	c.46+293A>C		intron	N/A	ENSP00000487291.1	A0A0D9SGA5

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 119618 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 62036

African (AFR) AF: 0.00 AC: 0 AN: 2944

American (AMR) AF: 0.00 AC: 0 AN: 3182

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4266

East Asian (EAS) AF: 0.00 AC: 0 AN: 7464

South Asian (SAS) AF: 0.00 AC: 0 AN: 9674

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8034

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 610

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 75830

Other (OTH) AF: 0.00 AC: 0 AN: 7614

GnomAD4 genome Cov.: 23

Alfa AF: 0.00 Hom.: 951

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.9
DANN	Benign	0.49
PhyloP100		-0.027
PromoterAI		0.074	Neutral

Splicing

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

Other links and lift over

dbSNP: rs6130997; hg19: chr20-44650818;