20-46022943-GGGAGGAGGAGGAGGAGGAGGAGGA-GGGAGGAGGAGGAGGAGGAGGAGGAGGAGGA

Variant names:

• chr20-46022943-G-GGGAGGA
• rs34923327
• ENST00000626701.1:c.250_255dupGGAGGA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001134771.2(SLC12A5):​c.121+1085_121+1090dupGGAGGA variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.087 (442 hom., cov: 0)
  • Exomes 𝑓: 0.11 (549 hom.)
• Consequence: SLC12A5 NM_001134771.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.07
• Publications: 0 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 Gene-Disease associations (from GenCC):

• developmental and epileptic encephalopathy, 34

  Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, Illumina, Labcorp Genetics (formerly Invitae)
• epilepsy of infancy with migrating focal seizures

  Inheritance: AR Classification: STRONG Submitted by: G2P
• malignant migrating partial seizures of infancy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• epilepsy, idiopathic generalized, susceptibility to, 14

  Inheritance: AD Classification: LIMITED, NO_KNOWN Submitted by: Ambry Genetics, Illumina
• genetic developmental and epileptic encephalopathy

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 20-46022943-G-GGGAGGA is Benign according to our data. Variant chr20-46022943-G-GGGAGGA is described in ClinVar as Benign. ClinVar VariationId is 3911459.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.

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+1085_121+1090dupGGAGGA		intron	N/A	NP_001128243.1	Q9H2X9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC12A5	ENST00000626701.1	TSL:3	c.250_255dupGGAGGA	p.Gly84_Gly85dup	conservative_inframe_insertion	Exon 2 of 3	ENSP00000487372.1	A0A0D9SGD0
	SLC12A5	ENST00000413737.2	TSL:3	c.88_93dupGGAGGA	p.Gly30_Gly31dup	conservative_inframe_insertion	Exon 2 of 3	ENSP00000487291.1	A0A0D9SGA5
	SLC12A5	ENST00000454036.6	TSL:5	c.121+1085_121+1090dupGGAGGA		intron	N/A	ENSP00000387694.1	Q9H2X9-1

Frequencies

GnomAD3 genomes AF: 0.0868 AC: 10467 AN: 120520 Hom.: 443 Cov.: 0

Gnomad AFR AF: 0.0488

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.0469

Gnomad ASJ AF: 0.0605

Gnomad EAS AF: 0.0504

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.0993

Gnomad MID AF: 0.0675

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.0635

GnomAD4 exome AF: 0.114 AC: 27726 AN: 243368 Hom.: 549 Cov.: 0 AF XY: 0.115 AC XY: 14281 AN XY: 124566

African (AFR) AF: 0.0597 AC: 404 AN: 6764

American (AMR) AF: 0.0519 AC: 377 AN: 7258

Ashkenazi Jewish (ASJ) AF: 0.0826 AC: 742 AN: 8984

East Asian (EAS) AF: 0.105 AC: 2340 AN: 22188

South Asian (SAS) AF: 0.160 AC: 474 AN: 2958

European-Finnish (FIN) AF: 0.118 AC: 2407 AN: 20320

Middle Eastern (MID) AF: 0.0921 AC: 116 AN: 1260

European-Non Finnish (NFE) AF: 0.122 AC: 19262 AN: 157596

Other (OTH) AF: 0.100 AC: 1604 AN: 16040

GnomAD4 genome AF: 0.0868 AC: 10472 AN: 120580 Hom.: 442 Cov.: 0 AF XY: 0.0837 AC XY: 4832 AN XY: 57700

African (AFR) AF: 0.0489 AC: 1364 AN: 27898

American (AMR) AF: 0.0468 AC: 581 AN: 12404

Ashkenazi Jewish (ASJ) AF: 0.0605 AC: 186 AN: 3072

East Asian (EAS) AF: 0.0508 AC: 216 AN: 4256

South Asian (SAS) AF: 0.134 AC: 468 AN: 3500

European-Finnish (FIN) AF: 0.0993 AC: 776 AN: 7814

Middle Eastern (MID) AF: 0.0726 AC: 17 AN: 234

European-Non Finnish (NFE) AF: 0.113 AC: 6662 AN: 58940

Other (OTH) AF: 0.0642 AC: 109 AN: 1698

Alfa AF: 0.0484 Hom.: 174

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs34923327; hg19: chr20-44651582; COSMIC: COSV69557158; COSMIC: COSV69557158;