NM_020208.4:c.582+639G>A

Variant names:

• chr3-45775122-C-T
• rs13062383
• NM_020208.4:c.582+639G>A

Variant summary

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

The NM_020208.4(SLC6A20):​c.582+639G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0741 in 152,104 control chromosomes in the GnomAD database, including 502 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 0.074 (502 hom., cov: 32)
• Consequence: SLC6A20 NM_020208.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.190
• Publications: 9 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A20	NM_020208.4	c.582+639G>A		intron_variant	Intron 4 of 10	ENST00000358525.9	NP_064593.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC6A20	ENST00000358525.9	c.582+639G>A		intron_variant	Intron 4 of 10	1	NM_020208.4	ENSP00000346298.4

Frequencies

GnomAD3 genomes AF: 0.0741 AC: 11266 AN: 151986 Hom.: 501 Cov.: 32

Gnomad AFR AF: 0.0226

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.0800

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.0828

Gnomad FIN AF: 0.0723

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0956

Gnomad OTH AF: 0.0827

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

GnomAD4 genome AF: 0.0741 AC: 11268 AN: 152104 Hom.: 502 Cov.: 32 AF XY: 0.0729 AC XY: 5424 AN XY: 74360

African (AFR) AF: 0.0226 AC: 936 AN: 41478

American (AMR) AF: 0.0804 AC: 1228 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.106 AC: 368 AN: 3468

East Asian (EAS) AF: 0.150 AC: 776 AN: 5176

South Asian (SAS) AF: 0.0829 AC: 399 AN: 4814

European-Finnish (FIN) AF: 0.0723 AC: 765 AN: 10586

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0956 AC: 6500 AN: 67986

Other (OTH) AF: 0.0823 AC: 174 AN: 2114

Alfa AF: 0.0877 Hom.: 1011

Bravo AF: 0.0719

Asia WGS AF: 0.0980 AC: 340 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.2
DANN	Benign	0.74
PhyloP100		-0.19
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: rs13062383; hg19: chr3-45816614;