Variant 1-110192212-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate

The NM_001010898.4(SLC6A17):c.1105G>C(p.Glu369Gln) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000000688 in 1,454,454 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. 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. E369K) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

SLC6A17
NM_001010898.4 missense, splice_region

Scores

Splicing: ADA: 0.01932

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.40

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), SLC6A17. . Gene score misZ 2.3852 (greater than the threshold 3.09). Trascript score misZ 3.6036 (greater than threshold 3.09). GenCC has associacion of gene with progressive essential tremor-speech impairment-facial dysmorphism-intellectual disability-abnormal behavior syndrome, schizophrenia.

BP4

Computational evidence support a benign effect (MetaRNN=0.18922737).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC6A17	NM_001010898.4 linkuse as main transcript	c.1105G>C	p.Glu369Gln	missense_variant, splice_region_variant	7/12	ENST00000331565.5	NP_001010898.1	Q9H1V8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC6A17	ENST00000331565.5 linkuse as main transcript	c.1105G>C	p.Glu369Gln	missense_variant, splice_region_variant	7/12	2	NM_001010898.4	ENSP00000330199.3		Q9H1V8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000403

AC:

AN:

248312

Hom.:

AF XY:

0.00000746

AC XY:

AN XY:

134122

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000893

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.88e-7

AC:

AN:

1454454

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

722110

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.04e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.46

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0082

Eigen

Benign

-0.18

Eigen_PC

Benign

0.046

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.84

M_CAP

Benign

0.0090

MetaRNN

Benign

0.19

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.28

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-0.18

REVEL

Benign

0.13

Sift

Benign

0.46

Sift4G

Benign

0.58

Polyphen

0.030

Vest4

0.27

MutPred

0.51

Loss of helix (P = 0.0093);

MVP

0.35

MPC

0.58

ClinPred

0.43

GERP RS

4.7

Varity_R

0.13

gMVP

0.62

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.019

dbscSNV1_RF

Benign

0.068

SpliceAI score (max)

0.15

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over