3-45793319-G-T

Variant names:

• chr3-45793319-G-T
• rs13064991
• NM_020208.4:c.121+2980C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020208.4(SLC6A20):​c.121+2980C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 151,982 control chromosomes in the GnomAD database, including 2,509 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 0.16 (2509 hom., cov: 32)
• Consequence: SLC6A20 NM_020208.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.23
• Publications: 7 publications found

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]

SLC6A20 Gene-Disease associations (from GenCC):

• hyperglycinuria

  Inheritance: AR, Unknown Classification: LIMITED, NO_KNOWN Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ENSG00000307655 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.431 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020208.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A20	NM_020208.4	MANE Select	c.121+2980C>A		intron	N/A	NP_064593.1
	SLC6A20	NM_001385683.1		c.121+2980C>A		intron	N/A	NP_001372612.1
	SLC6A20	NM_022405.4		c.121+2980C>A		intron	N/A	NP_071800.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A20	ENST00000358525.9	TSL:1 MANE Select	c.121+2980C>A		intron	N/A	ENSP00000346298.4
	SLC6A20	ENST00000353278.8	TSL:1	c.121+2980C>A		intron	N/A	ENSP00000296133.5
	SLC6A20	ENST00000703343.1		c.121+2980C>A		intron	N/A	ENSP00000515266.1

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24476 AN: 151864 Hom.: 2505 Cov.: 32

Gnomad AFR AF: 0.0789

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.275

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.446

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.166

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

GnomAD4 genome AF: 0.161 AC: 24489 AN: 151982 Hom.: 2509 Cov.: 32 AF XY: 0.165 AC XY: 12259 AN XY: 74258

African (AFR) AF: 0.0788 AC: 3272 AN: 41508

American (AMR) AF: 0.276 AC: 4217 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.121 AC: 418 AN: 3468

East Asian (EAS) AF: 0.446 AC: 2303 AN: 5160

South Asian (SAS) AF: 0.176 AC: 824 AN: 4676

European-Finnish (FIN) AF: 0.133 AC: 1410 AN: 10588

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.169 AC: 11521 AN: 67996

Other (OTH) AF: 0.165 AC: 348 AN: 2106

Alfa AF: 0.163 Hom.: 2829

Bravo AF: 0.165

Asia WGS AF: 0.266 AC: 919 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.011
DANN	Benign	0.41
PhyloP100		-3.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs13064991; hg19: chr3-45834811;