rs17671169

Variant names:

• chr1-110181223-G-A
• rs17671169
• NM_001010898.4:c.864+4484G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001010898.4(SLC6A17):​c.864+4484G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 152,052 control chromosomes in the GnomAD database, including 10,948 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.34 (10948 hom., cov: 32)
• Consequence: SLC6A17 NM_001010898.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0910
• Publications: 3 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 Gene-Disease associations (from GenCC):

• progressive essential tremor-speech impairment-facial dysmorphism-intellectual disability-abnormal behavior syndrome

  Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: G2P, Ambry Genetics, Illumina, Orphanet, Labcorp Genetics (formerly Invitae)
• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.466 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A17	NM_001010898.4	MANE Select	c.864+4484G>A		intron	N/A	NP_001010898.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A17	ENST00000331565.5	TSL:2 MANE Select	c.864+4484G>A		intron	N/A	ENSP00000330199.3

Frequencies

GnomAD3 genomes AF: 0.345 AC: 52415 AN: 151934 Hom.: 10952 Cov.: 32

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.484

Gnomad AMR AF: 0.304

Gnomad ASJ AF: 0.495

Gnomad EAS AF: 0.224

Gnomad SAS AF: 0.340

Gnomad FIN AF: 0.500

Gnomad MID AF: 0.344

Gnomad NFE AF: 0.471

Gnomad OTH AF: 0.357

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.345 AC: 52400 AN: 152052 Hom.: 10948 Cov.: 32 AF XY: 0.345 AC XY: 25655 AN XY: 74294

African (AFR) AF: 0.113 AC: 4701 AN: 41482

American (AMR) AF: 0.304 AC: 4640 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.495 AC: 1718 AN: 3468

East Asian (EAS) AF: 0.224 AC: 1161 AN: 5180

South Asian (SAS) AF: 0.340 AC: 1632 AN: 4804

European-Finnish (FIN) AF: 0.500 AC: 5273 AN: 10556

Middle Eastern (MID) AF: 0.339 AC: 99 AN: 292

European-Non Finnish (NFE) AF: 0.471 AC: 31988 AN: 67972

Other (OTH) AF: 0.355 AC: 747 AN: 2106

Alfa AF: 0.394 Hom.: 5813

Bravo AF: 0.318

Asia WGS AF: 0.267 AC: 929 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.32
PhyloP100		-0.091
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17671169; hg19: chr1-110723845;