rs6770261

Positions:

• chr3-45763242-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000358525.9(SLC6A20):​c.1304-170G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 152,034 control chromosomes in the GnomAD database, including 7,476 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.30 (7476 hom., cov: 32)
• Consequence: SLC6A20 ENST00000358525.9 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.43

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 3-45763242-C-T is Benign according to our data. Variant chr3-45763242-C-T is described in ClinVar as [Benign]. Clinvar id is 1244873.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.436 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC6A20	NM_020208.4	c.1304-170G>A		intron_variant		ENST00000358525.9	NP_064593.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC6A20	ENST00000358525.9	c.1304-170G>A		intron_variant		1	NM_020208.4	ENSP00000346298	P1

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45497 AN: 151916 Hom.: 7458 Cov.: 32

Gnomad AFR AF: 0.441

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.171

Gnomad SAS AF: 0.246

Gnomad FIN AF: 0.237

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.253

Gnomad OTH AF: 0.279

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

GnomAD4 genome AF: 0.300 AC: 45552 AN: 152034 Hom.: 7476 Cov.: 32 AF XY: 0.295 AC XY: 21894 AN XY: 74324

Gnomad4 AFR AF: 0.441

Gnomad4 AMR AF: 0.247

Gnomad4 ASJ AF: 0.252

Gnomad4 EAS AF: 0.170

Gnomad4 SAS AF: 0.246

Gnomad4 FIN AF: 0.237

Gnomad4 NFE AF: 0.253

Gnomad4 OTH AF: 0.286

Alfa AF: 0.253 Hom.: 6720

Bravo AF: 0.306

Asia WGS AF: 0.253 AC: 882 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 15, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.33
DANN	Benign	0.55

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: rs6770261; hg19: chr3-45804734;