3-45762577-C-T

Variant names:

• chr3-45762577-C-T
• rs2286489
• NM_020208.4:c.1463+336G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001385683.1(SLC6A20):​c.1496+336G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.567 in 152,176 control chromosomes in the GnomAD database, including 25,575 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.57 (25575 hom., cov: 33)
• Consequence: SLC6A20 NM_001385683.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.892
• Publications: 5 publications found

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 Gene-Disease associations (from GenCC):

• hyperglycinuria

  Inheritance: AR, Unknown Classification: LIMITED, NO_KNOWN Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.659 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001385683.1. 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
	SLC6A20	NM_020208.4	MANE Select	c.1463+336G>A		intron	N/A	NP_064593.1
	SLC6A20	NM_001385683.1		c.1496+336G>A		intron	N/A	NP_001372612.1
	SLC6A20	NM_022405.4		c.1352+336G>A		intron	N/A	NP_071800.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A20	ENST00000358525.9	TSL:1 MANE Select	c.1463+336G>A		intron	N/A	ENSP00000346298.4
	SLC6A20	ENST00000353278.8	TSL:1	c.1352+336G>A		intron	N/A	ENSP00000296133.5
	SLC6A20	ENST00000473146.5	TSL:1	n.1651+336G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.567 AC: 86255 AN: 152058 Hom.: 25582 Cov.: 33

Gnomad AFR AF: 0.383

Gnomad AMI AF: 0.652

Gnomad AMR AF: 0.664

Gnomad ASJ AF: 0.598

Gnomad EAS AF: 0.575

Gnomad SAS AF: 0.679

Gnomad FIN AF: 0.676

Gnomad MID AF: 0.782

Gnomad NFE AF: 0.628

Gnomad OTH AF: 0.588

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.567 AC: 86277 AN: 152176 Hom.: 25575 Cov.: 33 AF XY: 0.576 AC XY: 42838 AN XY: 74396

African (AFR) AF: 0.383 AC: 15885 AN: 41504

American (AMR) AF: 0.664 AC: 10158 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.598 AC: 2074 AN: 3468

East Asian (EAS) AF: 0.575 AC: 2981 AN: 5180

South Asian (SAS) AF: 0.679 AC: 3276 AN: 4826

European-Finnish (FIN) AF: 0.676 AC: 7158 AN: 10596

Middle Eastern (MID) AF: 0.779 AC: 229 AN: 294

European-Non Finnish (NFE) AF: 0.628 AC: 42689 AN: 67984

Other (OTH) AF: 0.583 AC: 1232 AN: 2114

Alfa AF: 0.620 Hom.: 49342

Bravo AF: 0.553

Asia WGS AF: 0.587 AC: 2038 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.3
DANN	Benign	0.53
PhyloP100		0.89
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs2286489; hg19: chr3-45804069;