3-45756293-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_020208.4(SLC6A20):c.*2685T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.965 in 152,396 control chromosomes in the GnomAD database, including 70,909 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.96 (70872 hom., cov: 32)
  • Exomes 𝑓: 0.99 (37 hom.)
• Consequence: SLC6A20 NM_020208.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.917

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 3-45756293-A-G is Benign according to our data. Variant chr3-45756293-A-G is described in ClinVar as [Benign]. Clinvar id is 345349.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.979 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC6A20	NM_020208.4	c.*2685T>C		3_prime_UTR_variant	11/11	ENST00000358525.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC6A20	ENST00000358525.9	c.*2685T>C		3_prime_UTR_variant	11/11	1	NM_020208.4	P1
SLC6A20	ENST00000353278.8	c.*2685T>C		3_prime_UTR_variant	10/10	1

Frequencies

GnomAD3 genomes AF: 0.965 AC: 146809 AN: 152202 Hom.: 70819 Cov.: 32

Gnomad AFR AF: 0.987

Gnomad AMI AF: 0.915

Gnomad AMR AF: 0.974

Gnomad ASJ AF: 0.987

Gnomad EAS AF: 0.915

Gnomad SAS AF: 0.980

Gnomad FIN AF: 0.940

Gnomad MID AF: 0.991

Gnomad NFE AF: 0.955

Gnomad OTH AF: 0.963

GnomAD4 exome AF: 0.987 AC: 75 AN: 76 Hom.: 37 Cov.: 0 AF XY: 1.00 AC XY: 52 AN XY: 52

Gnomad4 AFR exome AF: 1.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.984

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.965 AC: 146922 AN: 152320 Hom.: 70872 Cov.: 32 AF XY: 0.965 AC XY: 71853 AN XY: 74496

Gnomad4 AFR AF: 0.987

Gnomad4 AMR AF: 0.973

Gnomad4 ASJ AF: 0.987

Gnomad4 EAS AF: 0.916

Gnomad4 SAS AF: 0.981

Gnomad4 FIN AF: 0.940

Gnomad4 NFE AF: 0.955

Gnomad4 OTH AF: 0.964

Alfa AF: 0.960 Hom.: 65783

Bravo AF: 0.966

Asia WGS AF: 0.943 AC: 3280 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Hyperglycinuria Benign:1

Benign, 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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.93
Dann	Benign	0.35

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: rs2742388; hg19: chr3-45797785;