1-110167097-T-A

Variant names:

• chr1-110167097-T-A
• rs7527375
• NM_001010898.4:c.168T>A

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.168T>A​(p.Asp56Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000668 in 149,690 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. D56D) has been classified as Benign.

• Frequency: Genomes: 𝑓 0.0000067 (0 hom., cov: 24)
• Consequence: SLC6A17 NM_001010898.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.63
• Publications: 9 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=0.030487418).

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.168T>A	p.Asp56Glu	missense	Exon 2 of 12	NP_001010898.1	Q9H1V8
	SLC6A17-AS1	NR_183667.1		n.522A>T		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.168T>A	p.Asp56Glu	missense	Exon 2 of 12	ENSP00000330199.3	Q9H1V8
	SLC6A17-AS1	ENST00000430098.2	TSL:1	n.522A>T		non_coding_transcript_exon	Exon 2 of 3
	SLC6A17	ENST00000873463.1		c.168T>A	p.Asp56Glu	missense	Exon 2 of 12	ENSP00000543522.1

Frequencies

GnomAD3 genomes AF: 0.00000668 AC: 1 AN: 149690 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.0000247

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 73

GnomAD4 genome AF: 0.00000668 AC: 1 AN: 149690 Hom.: 0 Cov.: 24 AF XY: 0.0000137 AC XY: 1 AN XY: 72902

African (AFR) AF: 0.0000247 AC: 1 AN: 40538

American (AMR) AF: 0.00 AC: 0 AN: 15078

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3456

East Asian (EAS) AF: 0.00 AC: 0 AN: 5074

South Asian (SAS) AF: 0.00 AC: 0 AN: 4612

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10314

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67378

Other (OTH) AF: 0.00 AC: 0 AN: 2026

Alfa AF: 0.00 Hom.: 7476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	0.013
DANN	Benign	0.72
DEOGEN2	Benign	0.0069	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.032	N
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.030	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-0.090	N
PhyloP100		-5.6
PrimateAI	Benign	0.47	T
PROVEAN	Benign	0.040	N
REVEL	Benign	0.072
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.12
MutPred		0.26		Gain of disorder (P = 0.1569)
MVP		0.20
MPC		0.52
ClinPred		0.11	T
GERP RS		-7.0
Varity_R		0.030
gMVP		0.088
Mutation Taster		=93/7	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: rs7527375; hg19: chr1-110709719;