11-62979839-G-A

Variant summary

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

The NM_153276.3(SLC22A6):c.1147C>T(p.Leu383Phe) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC22A6 NM_153276.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.669

Genes affected

SLC22A6 (HGNC:10970): (solute carrier family 22 member 6) The protein encoded by this gene is involved in the sodium-dependent transport and excretion of organic anions, some of which are potentially toxic. The encoded protein is an integral membrane protein and may be localized to the basolateral membrane. Four transcript variants encoding four different isoforms have been found for this gene. [provided by RefSeq, Jul 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=0.08938247).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC22A6	NM_153276.3	c.1147C>T	p.Leu383Phe	missense_variant	7/10	ENST00000360421.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC22A6	ENST00000360421.9	c.1147C>T	p.Leu383Phe	missense_variant	7/10	1	NM_153276.3	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 10, 2022

The c.1147C>T (p.L383F) alteration is located in exon 7 (coding exon 7) of the SLC22A6 gene. This alteration results from a C to T substitution at nucleotide position 1147, causing the leucine (L) at amino acid position 383 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
Cadd	Benign	11
Dann	Benign	0.94
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.61	T;T;T;T
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.089	T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.1	L;L;L;L
MutationTaster	Benign	0.69	D;D;D;D
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.98	N;N;N;N
REVEL	Benign	0.080
Sift	Benign	0.49	T;T;T;T
Sift4G	Benign	0.48	T;T;T;T
Polyphen		0.0030	B;B;B;B
Vest4		0.12
MutPred		0.49		Gain of methylation at K382 (P = 0.0283);Gain of methylation at K382 (P = 0.0283);Gain of methylation at K382 (P = 0.0283);Gain of methylation at K382 (P = 0.0283);
MVP		0.35
MPC		0.19
ClinPred		0.20	T
GERP RS		1.5
Varity_R		0.075
gMVP		0.29

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-62747311;