1-110167098-G-C

Variant names:

• chr1-110167098-G-C
• rs12737742
• NM_001010898.4:c.169G>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001010898.4(SLC6A17):​c.169G>C​(p.Ala57Pro) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A57T) has been classified as Benign.

• Frequency: Genomes: not found (cov: 25)
• Consequence: SLC6A17 NM_001010898.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.681

Genes affected

SLC6A17 (HGNC:31399): (solute carrier family 6 member 17) The protein encoded by this gene is a member of the SLC6 family of transporters, which are responsible for the presynaptic uptake of most neurotransmitters. The encoded vesicular transporter is selective for proline, glycine, leucine and alanine. In mouse, the strongest expression of this gene was in cortical and hippocampal tissues where expression increased during embryonic brain development and peaked postnatally. Defects in this gene cause a form of autosomal recessive intellectual disability. [provided by RefSeq, Jul 2017]

SLC6A17-AS1 (HGNC:41279): (SLC6A17 antisense RNA 1)

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04333666).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A17	NM_001010898.4	c.169G>C	p.Ala57Pro	missense_variant	Exon 2 of 12	ENST00000331565.5	NP_001010898.1
SLC6A17-AS1	NR_183667.1	n.521C>G		non_coding_transcript_exon_variant	Exon 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC6A17	ENST00000331565.5	c.169G>C	p.Ala57Pro	missense_variant	Exon 2 of 12	2	NM_001010898.4	ENSP00000330199.3
SLC6A17-AS1	ENST00000430098.2	n.521C>G		non_coding_transcript_exon_variant	Exon 2 of 3	1
SLC6A17-AS1	ENST00000418579.1	n.167C>G		non_coding_transcript_exon_variant	Exon 2 of 2	3
SLC6A17-AS1	ENST00000443008.1	n.506C>G		non_coding_transcript_exon_variant	Exon 2 of 2	3

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome Cov.: 72

GnomAD4 genome Cov.: 25

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	12
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0079	T
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.043	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.28	N
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.17	N
REVEL	Benign	0.075
Sift	Benign	0.27	T
Sift4G	Benign	0.34	T
Polyphen		0.0	B
Vest4		0.28
MutPred		0.29		Gain of glycosylation at A57 (P = 0.0774);
MVP		0.47
MPC		0.94
ClinPred		0.10	T
GERP RS		2.6
Varity_R		0.065
gMVP		0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs12737742; hg19: chr1-110709720;