1-110167098-G-C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -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. 16/22 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
• Publications: 21 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001010898.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A17	NM_001010898.4	MANE Select	c.169G>C	p.Ala57Pro	missense	Exon 2 of 12	NP_001010898.1	Q9H1V8
	SLC6A17-AS1	NR_183667.1		n.521C>G		non_coding_transcript_exon	Exon 2 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A17	ENST00000331565.5	TSL:2 MANE Select	c.169G>C	p.Ala57Pro	missense	Exon 2 of 12	ENSP00000330199.3	Q9H1V8
	SLC6A17-AS1	ENST00000430098.2	TSL:1	n.521C>G		non_coding_transcript_exon	Exon 2 of 3
	SLC6A17	ENST00000873463.1		c.169G>C	p.Ala57Pro	missense	Exon 2 of 12	ENSP00000543522.1

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome Cov.: 72

GnomAD4 genome Cov.: 25

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		0.68
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
Mutation Taster		=92/8	polymorphism

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

Other links and lift over

dbSNP: rs12737742; hg19: chr1-110709720;