20-46022943-GGGAGGAGGAGGAGGAGGAGGAGGA-GGGAGGAGGAGGAGGAGGAGGAGGAGGA

Variant names:

• chr20-46022943-G-GGGA
• rs34923327
• ENST00000626701.1:c.253_255dupGGA

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+1088_121+1090dupGGA variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.19 (2226 hom., cov: 0)
  • Exomes 𝑓: 0.19 (1350 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-GGGA is Benign according to our data. Variant chr20-46022943-G-GGGA is described in ClinVar as Benign. ClinVar VariationId is 3911460.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.408 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+1088_121+1090dupGGA		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.253_255dupGGA	p.Gly85dup	conservative_inframe_insertion	Exon 2 of 3	ENSP00000487372.1	A0A0D9SGD0
	SLC12A5	ENST00000413737.2	TSL:3	c.91_93dupGGA	p.Gly31dup	conservative_inframe_insertion	Exon 2 of 3	ENSP00000487291.1	A0A0D9SGA5
	SLC12A5	ENST00000454036.6	TSL:5	c.121+1088_121+1090dupGGA		intron	N/A	ENSP00000387694.1	Q9H2X9-1

Frequencies

GnomAD3 genomes AF: 0.187 AC: 22669 AN: 120950 Hom.: 2226 Cov.: 0

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.239

Gnomad EAS AF: 0.424

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.192

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.185

GnomAD4 exome AF: 0.191 AC: 46398 AN: 242938 Hom.: 1350 Cov.: 0 AF XY: 0.189 AC XY: 23454 AN XY: 124416

African (AFR) AF: 0.173 AC: 1173 AN: 6788

American (AMR) AF: 0.130 AC: 948 AN: 7272

Ashkenazi Jewish (ASJ) AF: 0.228 AC: 2048 AN: 8966

East Asian (EAS) AF: 0.303 AC: 6705 AN: 22094

South Asian (SAS) AF: 0.222 AC: 653 AN: 2942

European-Finnish (FIN) AF: 0.201 AC: 4076 AN: 20286

Middle Eastern (MID) AF: 0.181 AC: 231 AN: 1276

European-Non Finnish (NFE) AF: 0.175 AC: 27542 AN: 157328

Other (OTH) AF: 0.189 AC: 3022 AN: 15986

GnomAD4 genome AF: 0.187 AC: 22675 AN: 121008 Hom.: 2226 Cov.: 0 AF XY: 0.191 AC XY: 11067 AN XY: 57882

African (AFR) AF: 0.177 AC: 4937 AN: 27922

American (AMR) AF: 0.144 AC: 1790 AN: 12416

Ashkenazi Jewish (ASJ) AF: 0.239 AC: 737 AN: 3080

East Asian (EAS) AF: 0.424 AC: 1803 AN: 4254

South Asian (SAS) AF: 0.227 AC: 797 AN: 3504

European-Finnish (FIN) AF: 0.172 AC: 1346 AN: 7836

Middle Eastern (MID) AF: 0.194 AC: 45 AN: 232

European-Non Finnish (NFE) AF: 0.181 AC: 10723 AN: 59292

Other (OTH) AF: 0.183 AC: 312 AN: 1704

Alfa AF: 0.0977 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;