20-46022943-G-GGGAGGAGGAGGAGGA

Position:

• chr20-46022943-G-GGGAGGAGGAGGAGGA

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP3 BP6_Moderate BS1 BS2

The ENST00000626701.1(SLC12A5):​c.241_255dup​(p.Gly81_Gly85dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0068 (7 hom., cov: 0)
  • Exomes 𝑓: 0.0087 (14 hom.)
• Consequence: SLC12A5 ENST00000626701.1 inframe_insertion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.07

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]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP3: Nonframeshift variant in repetitive region in ENST00000626701.1
• BP6: Variant 20-46022943-G-GGGAGGAGGAGGAGGA is Benign according to our data. Variant chr20-46022943-G-GGGAGGAGGAGGAGGA is described in ClinVar as [Likely_benign]. Clinvar id is 2652359.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00679 (821/120870) while in subpopulation NFE AF= 0.00862 (510/59132). AF 95% confidence interval is 0.00801. There are 7 homozygotes in gnomad4. There are 347 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC12A5	NM_001134771.2	c.121+1076_121+1090dup		intron_variant			NP_001128243.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC12A5	ENST00000413737.2	c.81_95dup	p.Gly28_Gly32dup	inframe_insertion	2/3	3		ENSP00000487291
SLC12A5	ENST00000626701.1	c.241_255dup	p.Gly81_Gly85dup	inframe_insertion	2/3	3		ENSP00000487372
SLC12A5	ENST00000454036.6	c.121+1076_121+1090dup		intron_variant		5		ENSP00000387694	P3

Frequencies

GnomAD3 genomes AF: 0.00680 AC: 822 AN: 120812 Hom.: 7 Cov.: 0

Gnomad AFR AF: 0.00629

Gnomad AMI AF: 0.00390

Gnomad AMR AF: 0.00556

Gnomad ASJ AF: 0.00520

Gnomad EAS AF: 0.00304

Gnomad SAS AF: 0.00368

Gnomad FIN AF: 0.00127

Gnomad MID AF: 0.00794

Gnomad NFE AF: 0.00862

Gnomad OTH AF: 0.00653

GnomAD4 exome AF: 0.00872 AC: 2120 AN: 243176 Hom.: 14 Cov.: 0 AF XY: 0.00860 AC XY: 1071 AN XY: 124572

Gnomad4 AFR exome AF: 0.00769

Gnomad4 AMR exome AF: 0.00843

Gnomad4 ASJ exome AF: 0.00637

Gnomad4 EAS exome AF: 0.00148

Gnomad4 SAS exome AF: 0.00370

Gnomad4 FIN exome AF: 0.00377

Gnomad4 NFE exome AF: 0.0105

Gnomad4 OTH exome AF: 0.00961

GnomAD4 genome AF: 0.00679 AC: 821 AN: 120870 Hom.: 7 Cov.: 0 AF XY: 0.00600 AC XY: 347 AN XY: 57844

Gnomad4 AFR AF: 0.00627

Gnomad4 AMR AF: 0.00556

Gnomad4 ASJ AF: 0.00520

Gnomad4 EAS AF: 0.00304

Gnomad4 SAS AF: 0.00398

Gnomad4 FIN AF: 0.00127

Gnomad4 NFE AF: 0.00862

Gnomad4 OTH AF: 0.00589

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

SLC12A5: BS2 -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs34923327; hg19: chr20-44651582;