Variant rs7527375 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_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. 16/21 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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -5.63

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:

SLC6A17-AS1 (HGNC:41279): (SLC6A17 antisense RNA 1)

SLC6A17-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.030487418).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A17	NM_001010898.4 link	c.168T>A	p.Asp56Glu	missense_variant	Exon 2 of 12	ENST00000331565.5	NP_001010898.1	Q9H1V8
SLC6A17-AS1	NR_183667.1 link	n.522A>T		non_coding_transcript_exon_variant	Exon 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC6A17	ENST00000331565.5 link	c.168T>A	p.Asp56Glu	missense_variant	Exon 2 of 12	2	NM_001010898.4	ENSP00000330199.3	Q9H1V8
SLC6A17-AS1	ENST00000430098.2 link	n.522A>T		non_coding_transcript_exon_variant	Exon 2 of 3	1
SLC6A17-AS1	ENST00000418579.1 link	n.168A>T		non_coding_transcript_exon_variant	Exon 2 of 2	3
SLC6A17-AS1	ENST00000443008.1 link	n.507A>T		non_coding_transcript_exon_variant	Exon 2 of 2	3

Frequencies

GnomAD3 genomes

AF:

0.00000668

AC:

AN:

149690

Hom.:

Cov.:

show subpopulations

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.:

GnomAD4 genome

AF:

0.00000668

AC:

AN:

149690

Hom.:

Cov.:

AF XY:

0.0000137

AC XY:

AN XY:

72902

show subpopulations

Gnomad4 AFR

AF:

0.0000247

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.66

CADD

Benign

0.013

DANN

Benign

0.72

DEOGEN2

Benign

0.0069

Eigen

Benign

-1.9

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.032

LIST_S2

Benign

0.35

M_CAP

Benign

0.030

MetaRNN

Benign

0.030

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-0.090

PrimateAI

Benign

0.47

PROVEAN

Benign

0.040

REVEL

Benign

0.072

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.12

MutPred

0.26

Gain of disorder (P = 0.1569);

MVP

0.20

MPC

0.52

ClinPred

0.11

GERP RS

-7.0

Varity_R

0.030

gMVP

0.088

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

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