1-110174904-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 1P and 14B. PP2 BP4_Strong BP6_Moderate BS1 BS2

The NM_001010898.4(SLC6A17):c.697G>A(p.Val233Met) variant causes a missense change. The variant allele was found at a frequency of 0.000549 in 1,614,144 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00071 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00053 (6 hom.)
• Consequence: SLC6A17 NM_001010898.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.57

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• PP2: Missense variant where missense usually causes diseases, SLC6A17
• BP4: Computational evidence support a benign effect (MetaRNN=0.010053158).
• BP6: Variant 1-110174904-G-A is Benign according to our data. Variant chr1-110174904-G-A is described in ClinVar as [Benign]. Clinvar id is 713882.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000709 (108/152310) while in subpopulation EAS AF= 0.0193 (100/5180). AF 95% confidence interval is 0.0162. There are 1 homozygotes in gnomad4. There are 51 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC6A17	NM_001010898.4	c.697G>A	p.Val233Met	missense_variant	5/12	ENST00000331565.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC6A17	ENST00000331565.5	c.697G>A	p.Val233Met	missense_variant	5/12	2	NM_001010898.4	P1

Frequencies

GnomAD3 genomes AF: 0.000703 AC: 107 AN: 152192 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0193

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.00146 AC: 367 AN: 251374 Hom.: 7 AF XY: 0.00141 AC XY: 191 AN XY: 135860

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0190

Gnomad SAS exome AF: 0.000196

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000440

Gnomad OTH exome AF: 0.000978

GnomAD4 exome AF: 0.000532 AC: 778 AN: 1461834 Hom.: 6 Cov.: 31 AF XY: 0.000542 AC XY: 394 AN XY: 727212

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0169

Gnomad4 SAS exome AF: 0.000255

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000324

Gnomad4 OTH exome AF: 0.000795

GnomAD4 genome AF: 0.000709 AC: 108 AN: 152310 Hom.: 1 Cov.: 32 AF XY: 0.000685 AC XY: 51 AN XY: 74486

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0193

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.000945

Alfa AF: 0.000823 Hom.: 1

Bravo AF: 0.000918

ExAC AF: 0.00147 AC: 179

Asia WGS AF: 0.00202 AC: 7 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.24
Cadd	Uncertain	25
Dann	Uncertain	1.0
DEOGEN2	Benign	0.029	T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.91	D
MetaRNN	Benign	0.010	T
MetaSVM	Uncertain	-0.087	T
MutationAssessor	Uncertain	2.3	M
MutationTaster	Benign	0.99	D;D
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-0.63	N
REVEL	Uncertain	0.38
Sift	Benign	0.081	T
Sift4G	Benign	0.092	T
Polyphen		0.97	D
Vest4		0.31
MVP		0.73
MPC		0.64
ClinPred		0.076	T
GERP RS		4.4
Varity_R		0.16
gMVP		0.53

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: rs79143268; hg19: chr1-110717526;