rs17279437

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_020208.4(SLC6A20):c.596C>T(p.Thr199Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0894 in 1,612,876 control chromosomes in the GnomAD database, including 7,209 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.066 ( 424 hom., cov: 32)

Exomes 𝑓: 0.092 ( 6785 hom. )

Consequence

SLC6A20
NM_020208.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5O:1

Conservation

PhyloP100: 8.14

Variant links:

Genes affected

SLC6A20 (HGNC:30927): (solute carrier family 6 member 20) Transport of small hydrophilic substances across cell membranes is mediated by substrate-specific transporter proteins which have been classified into several families of related genes. The protein encoded by this gene belongs to the sodium:neurotransmitter symporter (SNF) family and functions as a proline transporter expressed in kidney and small intestine. Mutations in this gene are associated with Hyperglycinuria and Iminoglycinuria. [provided by RefSeq, Jul 2020]

SLC6A20 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006226331).

BP6

Variant 3-45772602-G-A is Benign according to our data. Variant chr3-45772602-G-A is described in ClinVar as [Benign]. Clinvar id is 4845.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-45772602-G-A is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0956 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A20	NM_020208.4 link	c.596C>T	p.Thr199Met	missense_variant	Exon 5 of 11	ENST00000358525.9	NP_064593.1	Q9NP91-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC6A20	ENST00000358525.9 link	c.596C>T	p.Thr199Met	missense_variant	Exon 5 of 11	1	NM_020208.4	ENSP00000346298.4	Q9NP91-1
SLC6A20	ENST00000353278.8 link	c.583-1144C>T		intron_variant	Intron 4 of 9	1		ENSP00000296133.5	Q9NP91-2
SLC6A20	ENST00000703343.1 link	c.596C>T	p.Thr199Met	missense_variant	Exon 5 of 11			ENSP00000515266.1	A0A8V8TQV4
SLC6A20	ENST00000413781.1 link	n.571C>T		non_coding_transcript_exon_variant	Exon 4 of 5	5

Frequencies

GnomAD3 genomes

AF:

0.0659

AC:

10025

AN:

152124

Hom.:

424

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0189

Gnomad AMI

AF:

0.0614

Gnomad AMR

AF:

0.0497

Gnomad ASJ

AF:

0.115

Gnomad EAS

AF:

0.00654

Gnomad SAS

AF:

0.0394

Gnomad FIN

AF:

0.100

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0976

Gnomad OTH

AF:

0.0492

GnomAD3 exomes

AF:

0.0717

AC:

17750

AN:

247566

Hom.:

744

AF XY:

0.0726

AC XY:

9748

AN XY:

134334

show subpopulations

Gnomad AFR exome

AF:

0.0173

Gnomad AMR exome

AF:

0.0466

Gnomad ASJ exome

AF:

0.116

Gnomad EAS exome

AF:

0.00491

Gnomad SAS exome

AF:

0.0383

Gnomad FIN exome

AF:

0.104

Gnomad NFE exome

AF:

0.0967

Gnomad OTH exome

AF:

0.0679

GnomAD4 exome

AF:

0.0918

AC:

134120

AN:

1460634

Hom.:

6785

Cov.:

AF XY:

0.0903

AC XY:

65619

AN XY:

726600

show subpopulations

Gnomad4 AFR exome

AF:

0.0132

Gnomad4 AMR exome

AF:

0.0471

Gnomad4 ASJ exome

AF:

0.115

Gnomad4 EAS exome

AF:

0.00912

Gnomad4 SAS exome

AF:

0.0404

Gnomad4 FIN exome

AF:

0.0997

Gnomad4 NFE exome

AF:

0.103

Gnomad4 OTH exome

AF:

0.0799

GnomAD4 genome

AF:

0.0659

AC:

10030

AN:

152242

Hom.:

424

Cov.:

AF XY:

0.0648

AC XY:

4826

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.0188

Gnomad4 AMR

AF:

0.0499

Gnomad4 ASJ

AF:

0.115

Gnomad4 EAS

AF:

0.00656

Gnomad4 SAS

AF:

0.0396

Gnomad4 FIN

AF:

0.100

Gnomad4 NFE

AF:

0.0976

Gnomad4 OTH

AF:

0.0487

Alfa

AF:

0.0853

Hom.:

1308

Bravo

AF:

0.0596

TwinsUK

AF:

0.0909

AC:

337

ALSPAC

AF:

0.102

AC:

392

ESP6500AA

AF:

0.0204

AC:

ESP6500EA

AF:

0.0994

AC:

837

ExAC

AF:

0.0702

AC:

8496

Asia WGS

AF:

0.0270

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hyperglycinuria

Benign:2Other:1

May 28, 2019

Mendelics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Dec 01, 2008

OMIM

Significance: Affects

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Mar 06, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 05, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 19033659, 21572414) -

SLC6A20-related disorder

Benign:1

Dec 04, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.087

BayesDel_noAF

Pathogenic

0.18

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.28

T;T;.

Eigen

Pathogenic

0.84

Eigen_PC

Pathogenic

0.74

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.99

D;D;D

MetaRNN

Benign

0.0062

T;T;T

MetaSVM

Benign

-0.43

MutationAssessor

Pathogenic

4.2

H;.;.

PrimateAI

Uncertain

0.52

PROVEAN

Pathogenic

-5.5

D;D;D

REVEL

Pathogenic

0.72

Sift

Pathogenic

0.0

D;D;D

Sift4G

Pathogenic

0.0

D;D;.

Polyphen

1.0

D;.;.

Vest4

0.58

MPC

0.88

ClinPred

0.079

GERP RS

5.3

Varity_R

0.84

gMVP

0.83

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