rs2159272

Positions:

• chr3-45788503-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020208.4(SLC6A20):​c.122-6280T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.539 in 152,010 control chromosomes in the GnomAD database, including 23,193 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 0.54 (23193 hom., cov: 32)
• Consequence: SLC6A20 NM_020208.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.263

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.688 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC6A20	NM_020208.4	c.122-6280T>C		intron_variant		ENST00000358525.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC6A20	ENST00000358525.9	c.122-6280T>C		intron_variant		1	NM_020208.4	P1

Frequencies

GnomAD3 genomes AF: 0.538 AC: 81790 AN: 151892 Hom.: 23142 Cov.: 32

Gnomad AFR AF: 0.694

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.612

Gnomad ASJ AF: 0.430

Gnomad EAS AF: 0.647

Gnomad SAS AF: 0.565

Gnomad FIN AF: 0.422

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.443

Gnomad OTH AF: 0.545

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

GnomAD4 genome AF: 0.539 AC: 81907 AN: 152010 Hom.: 23193 Cov.: 32 AF XY: 0.538 AC XY: 39960 AN XY: 74308

Gnomad4 AFR AF: 0.695

Gnomad4 AMR AF: 0.612

Gnomad4 ASJ AF: 0.430

Gnomad4 EAS AF: 0.647

Gnomad4 SAS AF: 0.564

Gnomad4 FIN AF: 0.422

Gnomad4 NFE AF: 0.443

Gnomad4 OTH AF: 0.550

Alfa AF: 0.475 Hom.: 27027

Bravo AF: 0.558

Asia WGS AF: 0.629 AC: 2189 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	5.4
DANN	Benign	0.82

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

Publications

LitVar

Other links and lift over

dbSNP: rs2159272; hg19: chr3-45829995;