Variant 20-46022977-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_ModerateBP6_Very_Strong

The ENST00000626701.1(SLC12A5):c.256A>G(p.Arg86Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 7/7 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 1 hom., cov: 19)

Exomes 𝑓: 0.0010 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SLC12A5
ENST00000626701.1 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.00

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.

BP4

Computational evidence support a benign effect (MetaRNN=0.13475034).

BP6

Variant 20-46022977-A-G is Benign according to our data. Variant chr20-46022977-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1686411.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC12A5	NM_001134771.2 linkuse as main transcript	c.121+1091A>G		intron_variant			NP_001128243.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	Protein	Appris	UniProt
SLC12A5	ENST00000626701.1 linkuse as main transcript	c.256A>G	p.Arg86Gly	missense_variant	2/3	3	ENSP00000487372
SLC12A5	ENST00000413737.2 linkuse as main transcript	c.97A>G	p.Arg33Gly	missense_variant	2/3	3	ENSP00000487291
SLC12A5	ENST00000454036.6 linkuse as main transcript	c.121+1091A>G		intron_variant		5	ENSP00000387694	P3	Q9H2X9-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

1510

AN:

79916

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0486

Gnomad AMI

AF:

0.00175

Gnomad AMR

AF:

0.0137

Gnomad ASJ

AF:

0.00599

Gnomad EAS

AF:

0.00163

Gnomad SAS

AF:

0.0164

Gnomad FIN

AF:

0.00815

Gnomad MID

AF:

0.00649

Gnomad NFE

AF:

0.00840

Gnomad OTH

AF:

0.00903

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00103

AC:

175

AN:

170292

Hom.:

Cov.:

AF XY:

0.00127

AC XY:

111

AN XY:

87460

show subpopulations

Gnomad4 AFR exome

AF:

0.00644

Gnomad4 AMR exome

AF:

0.00123

Gnomad4 ASJ exome

AF:

0.000332

Gnomad4 EAS exome

AF:

0.000157

Gnomad4 SAS exome

AF:

0.00151

Gnomad4 FIN exome

AF:

0.000414

Gnomad4 NFE exome

AF:

0.000917

Gnomad4 OTH exome

AF:

0.00160

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0189

AC:

1511

AN:

79934

Hom.:

Cov.:

AF XY:

0.0194

AC XY:

742

AN XY:

38256

show subpopulations

Gnomad4 AFR

AF:

0.0486

Gnomad4 AMR

AF:

0.0137

Gnomad4 ASJ

AF:

0.00599

Gnomad4 EAS

AF:

0.00163

Gnomad4 SAS

AF:

0.0164

Gnomad4 FIN

AF:

0.00815

Gnomad4 NFE

AF:

0.00840

Gnomad4 OTH

AF:

0.00894

Alfa

AF:

0.206

Hom.:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Mendelics

May 04, 2022

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.67

CADD

Benign

8.6

DANN

Benign

0.81

DEOGEN2

Benign

0.064

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.26

MetaRNN

Benign

0.13

MutationTaster

Benign

0.89

Sift4G

Benign

0.77

Vest4

0.16

MVP

0.25

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