NM_020708.5:c.1099G>T

Variant names:

• chr20-46043185-G-T
• rs778801242
• NM_020708.5:c.1099G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020708.5(SLC12A5):​c.1099G>T​(p.Val367Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: SLC12A5 NM_020708.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.46

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1666862).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC12A5	NM_020708.5	c.1099G>T	p.Val367Leu	missense_variant	Exon 9 of 26	ENST00000243964.7	NP_065759.1
SLC12A5	NM_001134771.2	c.1168G>T	p.Val390Leu	missense_variant	Exon 9 of 26		NP_001128243.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC12A5	ENST00000243964.7	c.1099G>T	p.Val367Leu	missense_variant	Exon 9 of 26	1	NM_020708.5	ENSP00000243964.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.090	T;.;.
Eigen	Benign	-0.10
Eigen_PC	Benign	0.054
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.89	D;D;D
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.17	T;T;T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	1.6	L;.;.
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.60	N;.;N
REVEL	Benign	0.060
Sift	Uncertain	0.018	D;.;D
Sift4G	Benign	0.083	T;T;T
Polyphen		0.0	B;.;B
Vest4		0.048
MutPred		0.23		Loss of methylation at K388 (P = 0.0725);.;.;
MVP		0.67
MPC		0.95
ClinPred		0.61	D
GERP RS		4.5
Varity_R		0.15
gMVP		0.86

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs778801242; hg19: chr20-44671824;