rs17078339

Variant names:

• chr3-45780945-A-G
• rs17078339
• NM_020208.4:c.263-845T>C

Variant summary

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

The NM_020208.4(SLC6A20):​c.263-845T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 152,180 control chromosomes in the GnomAD database, including 6,594 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 0.29 (6594 hom., cov: 33)
• Consequence: SLC6A20 NM_020208.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0300
• Publications: 8 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.468 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A20	NM_020208.4	c.263-845T>C		intron_variant	Intron 2 of 10	ENST00000358525.9	NP_064593.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC6A20	ENST00000358525.9	c.263-845T>C		intron_variant	Intron 2 of 10	1	NM_020208.4	ENSP00000346298.4

Frequencies

GnomAD3 genomes AF: 0.287 AC: 43679 AN: 152062 Hom.: 6583 Cov.: 33

Gnomad AFR AF: 0.261

Gnomad AMI AF: 0.378

Gnomad AMR AF: 0.364

Gnomad ASJ AF: 0.316

Gnomad EAS AF: 0.484

Gnomad SAS AF: 0.331

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.280

Gnomad OTH AF: 0.308

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

GnomAD4 genome AF: 0.287 AC: 43726 AN: 152180 Hom.: 6594 Cov.: 33 AF XY: 0.288 AC XY: 21431 AN XY: 74406

African (AFR) AF: 0.261 AC: 10836 AN: 41508

American (AMR) AF: 0.364 AC: 5570 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.316 AC: 1096 AN: 3470

East Asian (EAS) AF: 0.484 AC: 2507 AN: 5178

South Asian (SAS) AF: 0.331 AC: 1599 AN: 4830

European-Finnish (FIN) AF: 0.190 AC: 2009 AN: 10584

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.280 AC: 19027 AN: 67996

Other (OTH) AF: 0.306 AC: 645 AN: 2110

Alfa AF: 0.290 Hom.: 15113

Bravo AF: 0.295

Asia WGS AF: 0.360 AC: 1251 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.6
DANN	Benign	0.66
PhyloP100		0.030
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs17078339; hg19: chr3-45822437;