1-110167098-G-A

Position:

chr1-110167098-G-A

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 1P and 20B. PP2BP4_StrongBP6_Very_StrongBA1

The NM_001010898.4(SLC6A17):c.169G>A(p.Ala57Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.424 in 1,610,442 control chromosomes in the GnomAD database, including 153,741 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.34 ( 10392 hom., cov: 25)

Exomes 𝑓: 0.43 ( 143349 hom. )

Consequence

SLC6A17
NM_001010898.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.681

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

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=6.933941E-5).

BP6

Variant 1-110167098-G-A is Benign according to our data. Variant chr1-110167098-G-A is described in ClinVar as [Benign]. Clinvar id is 1333112.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-110167098-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.455 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC6A17	NM_001010898.4 linkuse as main transcript	c.169G>A	p.Ala57Thr	missense_variant	2/12	ENST00000331565.5	NP_001010898.1
SLC6A17-AS1	NR_183667.1 linkuse as main transcript	n.521C>T		non_coding_transcript_exon_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
SLC6A17	ENST00000331565.5 linkuse as main transcript	c.169G>A	p.Ala57Thr	missense_variant	2/12	2	NM_001010898.4	ENSP00000330199	P1
SLC6A17-AS1	ENST00000430098.2 linkuse as main transcript	n.521C>T		non_coding_transcript_exon_variant	2/3	1
SLC6A17-AS1	ENST00000443008.1 linkuse as main transcript	n.506C>T		non_coding_transcript_exon_variant	2/2	3
SLC6A17-AS1	ENST00000418579.1 linkuse as main transcript	n.167C>T		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes

AF:

0.336

AC:

50402

AN:

150100

Hom.:

10397

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0966

Gnomad AMI

AF:

0.462

Gnomad AMR

AF:

0.298

Gnomad ASJ

AF:

0.453

Gnomad EAS

AF:

0.222

Gnomad SAS

AF:

0.336

Gnomad FIN

AF:

0.535

Gnomad MID

AF:

0.303

Gnomad NFE

AF:

0.460

Gnomad OTH

AF:

0.340

GnomAD3 exomes

AF:

0.372

AC:

92386

AN:

248036

Hom.:

19083

AF XY:

0.383

AC XY:

51342

AN XY:

134016

show subpopulations

Gnomad AFR exome

AF:

0.0887

Gnomad AMR exome

AF:

0.211

Gnomad ASJ exome

AF:

0.453

Gnomad EAS exome

AF:

0.210

Gnomad SAS exome

AF:

0.346

Gnomad FIN exome

AF:

0.535

Gnomad NFE exome

AF:

0.456

Gnomad OTH exome

AF:

0.414

GnomAD4 exome

AF:

0.433

AC:

632925

AN:

1460224

Hom.:

143349

Cov.:

AF XY:

0.433

AC XY:

314689

AN XY:

726238

show subpopulations

Gnomad4 AFR exome

AF:

0.0813

Gnomad4 AMR exome

AF:

0.220

Gnomad4 ASJ exome

AF:

0.459

Gnomad4 EAS exome

AF:

0.251

Gnomad4 SAS exome

AF:

0.341

Gnomad4 FIN exome

AF:

0.534

Gnomad4 NFE exome

AF:

0.462

Gnomad4 OTH exome

AF:

0.419

GnomAD4 genome

AF:

0.335

AC:

50386

AN:

150218

Hom.:

10392

Cov.:

AF XY:

0.338

AC XY:

24755

AN XY:

73240

show subpopulations

Gnomad4 AFR

AF:

0.0964

Gnomad4 AMR

AF:

0.298

Gnomad4 ASJ

AF:

0.453

Gnomad4 EAS

AF:

0.222

Gnomad4 SAS

AF:

0.335

Gnomad4 FIN

AF:

0.535

Gnomad4 NFE

AF:

0.460

Gnomad4 OTH

AF:

0.338

Alfa

AF:

0.433

Hom.:

22848

Bravo

AF:

0.308

TwinsUK

AF:

0.452

AC:

1675

ALSPAC

AF:

0.455

AC:

1754

ESP6500AA

AF:

0.108

AC:

477

ESP6500EA

AF:

0.445

AC:

3831

ExAC

AF:

0.371

AC:

45076

Asia WGS

AF:

0.268

AC:

935

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0084

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.29

MetaRNN

Benign

0.000069

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.55

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.35

REVEL

Benign

0.083

Sift

Benign

0.55

Sift4G

Benign

0.44

Polyphen

0.049

Vest4

0.039

MPC

0.54

ClinPred

0.0035

GERP RS

2.6

Varity_R

0.027

gMVP

0.14

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over