rs4299518

chr3-45767781-T-C

Variant summary

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

The NM_020208.4(SLC6A20):c.1099-2040A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.38 in 152,008 control chromosomes in the GnomAD database, including 12,021 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 0.38 (12021 hom., cov: 32)
• Consequence: SLC6A20 NM_020208.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.343

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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.465 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC6A20	NM_020208.4	c.1099-2040A>G		intron_variant		ENST00000358525.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC6A20	ENST00000358525.9	c.1099-2040A>G		intron_variant		1	NM_020208.4	P1
SLC6A20	ENST00000353278.8	c.988-2040A>G		intron_variant		1
SLC6A20	ENST00000473146.5	n.1287-2040A>G		intron_variant, non_coding_transcript_variant		1
SLC6A20	ENST00000703343.1	c.1132-2040A>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.380 AC: 57744 AN: 151890 Hom.: 12018 Cov.: 32

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.508

Gnomad AMR AF: 0.403

Gnomad ASJ AF: 0.459

Gnomad EAS AF: 0.0399

Gnomad SAS AF: 0.344

Gnomad FIN AF: 0.448

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.469

Gnomad OTH AF: 0.398

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

GnomAD4 genome AF: 0.380 AC: 57783 AN: 152008 Hom.: 12021 Cov.: 32 AF XY: 0.377 AC XY: 27996 AN XY: 74322

Gnomad4 AFR AF: 0.245

Gnomad4 AMR AF: 0.403

Gnomad4 ASJ AF: 0.459

Gnomad4 EAS AF: 0.0399

Gnomad4 SAS AF: 0.345

Gnomad4 FIN AF: 0.448

Gnomad4 NFE AF: 0.469

Gnomad4 OTH AF: 0.401

Alfa AF: 0.454 Hom.: 21309

Bravo AF: 0.370

Asia WGS AF: 0.214 AC: 750 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	2.4
Dann	Benign	0.70

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: rs4299518; hg19: chr3-45809273;