11-22359432-C-A

Position:

• chr11-22359432-C-A

Variant summary

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

The NM_020346.3(SLC17A6):​c.478C>A​(p.Leu160Ile) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC17A6 NM_020346.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.770

Genes affected

SLC17A6 (HGNC:16703): (solute carrier family 17 member 6) Predicted to enable L-glutamate transmembrane transporter activity and neurotransmitter transmembrane transporter activity. Involved in neurotransmitter loading into synaptic vesicle. Predicted to be located in synaptic vesicle. Predicted to be active in excitatory synapse. Predicted to be integral component of synaptic vesicle membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC17A6 (HGNC:):

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=0.23729208).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC17A6	NM_020346.3	c.478C>A	p.Leu160Ile	missense_variant	4/12	ENST00000263160.4	NP_065079.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC17A6	ENST00000263160.4	c.478C>A	p.Leu160Ile	missense_variant	4/12	1	NM_020346.3	ENSP00000263160.3
SLC17A6	ENST00000534115.1	n.409C>A		non_coding_transcript_exon_variant	2/3	3
SLC17A6	ENST00000648880.1	n.-45C>A		upstream_gene_variant

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

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

Dec 03, 2021

The c.478C>A (p.L160I) alteration is located in exon 4 (coding exon 4) of the SLC17A6 gene. This alteration results from a C to A substitution at nucleotide position 478, causing the leucine (L) at amino acid position 160 to be replaced by an isoleucine (I). 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	0.14
BayesDel_addAF	Benign	-0.062	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	24
DANN	Benign	0.92
DEOGEN2	Benign	0.28	T
Eigen	Benign	-0.021
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.86	T
MutationAssessor	Uncertain	2.0	M
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	0.070	N
REVEL	Benign	0.17
Sift	Benign	0.89	T
Sift4G	Benign	0.57	T
Polyphen		0.0050	B
Vest4		0.45
MutPred		0.64		Gain of catalytic residue at L165 (P = 0.1019);
MVP		0.082
MPC		0.50
ClinPred		0.75	D
GERP RS		5.3
Varity_R		0.13
gMVP		0.39

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: rs1304262025; hg19: chr11-22380978;