Genetic Variant SLC12A5:p.Gly81_Gly85dup (chr20-46022943-G-GGGAGGAGGAGGAGGA) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_001134771.2(SLC12A5):c.121+1076_121+1090dupGGAGGAGGAGGAGGA variant causes a intron 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
NM_001134771.2 intron

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.07

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

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 rank	MANE	Protein	UniProt
SLC12A5	NM_001134771.2 link	c.121+1076_121+1090dupGGAGGAGGAGGAGGA		intron_variant	Intron 1 of 25		NP_001128243.1	Q9H2X9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	Protein	UniProt
SLC12A5	ENST00000626701.1 link	c.241_255dupGGAGGAGGAGGAGGA	p.Gly81_Gly85dup	conservative_inframe_insertion	Exon 2 of 3	3	ENSP00000487372.1	A0A0D9SGD0
SLC12A5	ENST00000413737.2 link	c.79_93dupGGAGGAGGAGGAGGA	p.Gly27_Gly31dup	conservative_inframe_insertion	Exon 2 of 3	3	ENSP00000487291.1	A0A0D9SGA5
SLC12A5	ENST00000454036.6 link	c.121+1076_121+1090dupGGAGGAGGAGGAGGA		intron_variant	Intron 1 of 25	5	ENSP00000387694.1	Q9H2X9-1

Frequencies

GnomAD3 genomes

AF:

0.00680

AC:

822

AN:

120812

Hom.:

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.00860

AC XY:

1071

AN XY:

124572

show subpopulations

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.:

Cov.:

AF XY:

0.00600

AC XY:

347

AN XY:

57844

show subpopulations

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

LINK: link

Submissions by phenotype

not provided

Benign:1

Mar 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

SLC12A5: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over