3-45755542-G-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_020208.4(SLC6A20):c.*3436C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000282 in 152,326 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00028 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SLC6A20 NM_020208.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.45

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BS2: High AC in GnomAd at 43 AD,Digenic gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC6A20	NM_020208.4	c.*3436C>G		3_prime_UTR_variant	11/11	ENST00000358525.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC6A20	ENST00000358525.9	c.*3436C>G		3_prime_UTR_variant	11/11	1	NM_020208.4	P1
SLC6A20	ENST00000353278.8	c.*3436C>G		3_prime_UTR_variant	10/10	1

Frequencies

GnomAD3 genomes AF: 0.000283 AC: 43 AN: 152208 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000514

Gnomad OTH AF: 0.000478

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 386 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 230

Gnomad4 AFR exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.000282 AC: 43 AN: 152326 Hom.: 0 Cov.: 32 AF XY: 0.000215 AC XY: 16 AN XY: 74490

Gnomad4 AFR AF: 0.000144

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000515

Gnomad4 OTH AF: 0.000473

Bravo AF: 0.000317

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Hyperglycinuria Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.056
Dann	Benign	0.37

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: rs569114783; hg19: chr3-45797034;