1-110167097-T-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_001010898.4(SLC6A17):c.168T>C(p.Asp56=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.509 in 1,609,682 control chromosomes in the GnomAD database, including 213,991 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.50 (18682 hom., cov: 24)
  • Exomes 𝑓: 0.51 (195309 hom.)
• Consequence: SLC6A17 NM_001010898.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -5.63

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 Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 1-110167097-T-C is Benign according to our data. Variant chr1-110167097-T-C is described in ClinVar as [Benign]. Clinvar id is 1333111.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-110167097-T-C is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-5.63 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.529 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC6A17	NM_001010898.4	c.168T>C	p.Asp56=	synonymous_variant	2/12	ENST00000331565.5
SLC6A17-AS1	NR_183667.1	n.522A>G		non_coding_transcript_exon_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC6A17	ENST00000331565.5	c.168T>C	p.Asp56=	synonymous_variant	2/12	2	NM_001010898.4	P1
SLC6A17-AS1	ENST00000430098.2	n.522A>G		non_coding_transcript_exon_variant	2/3	1
SLC6A17-AS1	ENST00000443008.1	n.507A>G		non_coding_transcript_exon_variant	2/2	3
SLC6A17-AS1	ENST00000418579.1	n.168A>G		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes AF: 0.496 AC: 74104 AN: 149478 Hom.: 18666 Cov.: 24

Gnomad AFR AF: 0.500

Gnomad AMI AF: 0.502

Gnomad AMR AF: 0.392

Gnomad ASJ AF: 0.485

Gnomad EAS AF: 0.223

Gnomad SAS AF: 0.357

Gnomad FIN AF: 0.589

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.534

Gnomad OTH AF: 0.471

GnomAD3 exomes AF: 0.451 AC: 111689 AN: 247750 Hom.: 26983 AF XY: 0.454 AC XY: 60761 AN XY: 133864

Gnomad AFR exome AF: 0.505

Gnomad AMR exome AF: 0.263

Gnomad ASJ exome AF: 0.486

Gnomad EAS exome AF: 0.210

Gnomad SAS exome AF: 0.364

Gnomad FIN exome AF: 0.587

Gnomad NFE exome AF: 0.532

Gnomad OTH exome AF: 0.487

GnomAD4 exome AF: 0.510 AC: 744414 AN: 1460088 Hom.: 195309 Cov.: 73 AF XY: 0.507 AC XY: 367963 AN XY: 726180

Gnomad4 AFR exome AF: 0.503

Gnomad4 AMR exome AF: 0.276

Gnomad4 ASJ exome AF: 0.491

Gnomad4 EAS exome AF: 0.252

Gnomad4 SAS exome AF: 0.360

Gnomad4 FIN exome AF: 0.590

Gnomad4 NFE exome AF: 0.537

Gnomad4 OTH exome AF: 0.506

GnomAD4 genome AF: 0.496 AC: 74153 AN: 149594 Hom.: 18682 Cov.: 24 AF XY: 0.491 AC XY: 35838 AN XY: 72920

Gnomad4 AFR AF: 0.500

Gnomad4 AMR AF: 0.392

Gnomad4 ASJ AF: 0.485

Gnomad4 EAS AF: 0.223

Gnomad4 SAS AF: 0.355

Gnomad4 FIN AF: 0.589

Gnomad4 NFE AF: 0.534

Gnomad4 OTH AF: 0.468

Alfa AF: 0.502 Hom.: 7476

Bravo AF: 0.482

Asia WGS AF: 0.311 AC: 1084 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Progressive essential tremor-speech impairment-facial dysmorphism-intellectual disability-abnormal behavior syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	0.086
Dann	Benign	0.62

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: rs7527375; hg19: chr1-110709719; COSMIC: COSV58991969;