20-46022965-GGAGGAGGAGGAAGAGGAGGAGGAGGAA-G

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP3 BP6_Moderate BS1

The ENST00000626701.1(SLC12A5):c.271_297del(p.Arg91_Gly99del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000139 in 251,148 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00053 (0 hom., cov: 28)
  • Exomes 𝑓: 0.00014 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SLC12A5 ENST00000626701.1 inframe_deletion
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.91

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 -7 ACMG points.

• BP3: Nonframeshift variant in repetitive region in ENST00000626701.1
• BP6: Variant 20-46022965-GGAGGAGGAGGAAGAGGAGGAGGAGGAA-G is Benign according to our data. Variant chr20-46022965-GGAGGAGGAGGAAGAGGAGGAGGAGGAA-G is described in ClinVar as [Benign]. Clinvar id is 1686324.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.000139 (35/251148) while in subpopulation MID AF= 0.00153 (2/1308). AF 95% confidence interval is 0.000271. There are 0 homozygotes in gnomad4_exome. There are 16 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC12A5	NM_001134771.2	c.121+1106_121+1132del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC12A5	ENST00000413737.2	c.111_137del	p.Arg38_Gly46del	inframe_deletion	2/3	3
SLC12A5	ENST00000626701.1	c.271_297del	p.Arg91_Gly99del	inframe_deletion	2/3	3
SLC12A5	ENST00000454036.6	c.121+1106_121+1132del		intron_variant		5		P3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 78 AN: 147982 Hom.: 0 Cov.: 28 FAILED QC

Gnomad AFR AF: 0.000150

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00196

Gnomad ASJ AF: 0.000887

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000642

Gnomad FIN AF: 0.000286

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000451

Gnomad OTH AF: 0.00197

GnomAD4 exome AF: 0.000139 AC: 35 AN: 251148 Hom.: 0 AF XY: 0.000123 AC XY: 16 AN XY: 130284

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000149

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000188

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000139

Gnomad4 OTH exome AF: 0.000303

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000527 AC: 78 AN: 148066 Hom.: 0 Cov.: 28 AF XY: 0.000513 AC XY: 37 AN XY: 72122

Gnomad4 AFR AF: 0.000150

Gnomad4 AMR AF: 0.00196

Gnomad4 ASJ AF: 0.000887

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000642

Gnomad4 FIN AF: 0.000286

Gnomad4 NFE AF: 0.000451

Gnomad4 OTH AF: 0.00196

Alfa AF: 0.000551 Hom.: 0

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Mendelics

May 04, 2022

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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: rs912238609; hg19: chr20-44651604;