20-46022977-A-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Moderate BP6_Moderate

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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00

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 Likely_benign. Variant got -4 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_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC12A5	NM_001134771.2	c.121+1091A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC12A5	ENST00000626701.1	c.256A>G	p.Arg86Gly	missense_variant	2/3	3
SLC12A5	ENST00000413737.2	c.97A>G	p.Arg33Gly	missense_variant	2/3	3
SLC12A5	ENST00000454036.6	c.121+1091A>G		intron_variant		5		P3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 1510 AN: 79916 Hom.: 1 Cov.: 19 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.: 0 Cov.: 0 AF XY: 0.00127 AC XY: 111 AN XY: 87460

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.: 1 Cov.: 19 AF XY: 0.0194 AC XY: 742 AN XY: 38256

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.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Mendelics

May 04, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
Cadd	Benign	8.6
Dann	Benign	0.81
DEOGEN2	Benign	0.064	T
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.26	T
MetaRNN	Benign	0.13	T
MutationTaster	Benign	0.89	D
Sift4G	Benign	0.77	T
Vest4		0.16
MVP		0.25

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs58366483; hg19: chr20-44651616; COSMIC: COSV69557083; COSMIC: COSV69557083;