rs41313405

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001010898.4(SLC6A17):c.2036A>G(p.Lys679Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0039 in 1,614,160 control chromosomes in the GnomAD database, including 51 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0057 ( 7 hom., cov: 33)

Exomes 𝑓: 0.0037 ( 44 hom. )

Consequence

SLC6A17
NM_001010898.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 4.75

Publications

7 publications found

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 Gene-Disease associations (from GenCC):

progressive essential tremor-speech impairment-facial dysmorphism-intellectual disability-abnormal behavior syndrome
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: Illumina, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, Orphanet, PanelApp Australia
schizophrenia
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

SLC6A17 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_001010898.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0035065114).

BP6

Variant 1-110198296-A-G is Benign according to our data. Variant chr1-110198296-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 376873.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 7 AR,Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001010898.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A17	NM_001010898.4	MANE Select	c.2036A>G	p.Lys679Arg	missense	Exon 12 of 12	NP_001010898.1	Q9H1V8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A17	ENST00000331565.5	TSL:2 MANE Select	c.2036A>G	p.Lys679Arg	missense	Exon 12 of 12	ENSP00000330199.3	Q9H1V8
	SLC6A17	ENST00000873463.1		c.2051A>G	p.Lys684Arg	missense	Exon 12 of 12	ENSP00000543522.1

Frequencies

GnomAD3 genomes

AF:

0.00573

AC:

872

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000410

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00157

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0373

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00610

Gnomad OTH

AF:

0.00334

GnomAD2 exomes

AF:

0.00561

AC:

1410

AN:

251398

AF XY:

0.00553

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.00202

Gnomad ASJ exome

AF:

0.00159

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0333

Gnomad NFE exome

AF:

0.00508

Gnomad OTH exome

AF:

0.00375

GnomAD4 exome

AF:

0.00371

AC:

5419

AN:

1461886

Hom.:

Cov.:

AF XY:

0.00381

AC XY:

2772

AN XY:

727246

show subpopulations

African (AFR)

AF:

0.000269

AC:

AN:

33480

American (AMR)

AF:

0.00195

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00161

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000348

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.0297

AC:

1585

AN:

53412

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00320

AC:

3553

AN:

1112012

Other (OTH)

AF:

0.00232

AC:

140

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

366

732

1097

1463

1829

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

152

228

304

380

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00573

AC:

872

AN:

152274

Hom.:

Cov.:

AF XY:

0.00685

AC XY:

510

AN XY:

74444

show subpopulations

African (AFR)

AF:

0.000409

AC:

AN:

41562

American (AMR)

AF:

0.00157

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00317

AC:

AN:

3468

East Asian (EAS)

AF:

0.000193

AC:

AN:

5174

South Asian (SAS)

AF:

0.000207

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0373

AC:

396

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00610

AC:

415

AN:

68000

Other (OTH)

AF:

0.00331

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

144

192

240

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00460

Hom.:

Bravo

AF:

0.00253

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00338

EpiControl

AF:

0.00255

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (4)

Progressive essential tremor-speech impairment-facial dysmorphism-intellectual disability-abnormal behavior syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.35

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.020

Eigen

Benign

-0.079

Eigen_PC

Benign

0.054

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.86

MetaRNN

Benign

0.0035

MetaSVM

Benign

-0.69

MutationAssessor

Uncertain

2.4

PhyloP100

4.8

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-1.2

REVEL

Benign

0.14

Sift

Uncertain

0.025

Sift4G

Benign

0.14

Varity_R

0.15

gMVP

0.51

Mutation Taster

=97/3

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over