NM_020208.4:c.1099-2040A>G

Variant names:

• chr3-45767781-T-C
• rs4299518
• NM_020208.4:c.1099-2040A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 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)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SLC6A20	NM_020208.4	c.1099-2040A>G		intron_variant	Intron 7 of 10	ENST00000358525.9	NP_064593.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC6A20	ENST00000358525.9	c.1099-2040A>G		intron_variant	Intron 7 of 10	1	NM_020208.4	ENSP00000346298.4
SLC6A20	ENST00000353278.8	c.988-2040A>G		intron_variant	Intron 6 of 9	1		ENSP00000296133.5
SLC6A20	ENST00000473146.5	n.1287-2040A>G		intron_variant	Intron 2 of 5	1
SLC6A20	ENST00000703343.1	c.1132-2040A>G		intron_variant	Intron 7 of 10			ENSP00000515266.1

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

African (AFR) AF: 0.245 AC: 10137 AN: 41458

American (AMR) AF: 0.403 AC: 6148 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.459 AC: 1592 AN: 3468

East Asian (EAS) AF: 0.0399 AC: 207 AN: 5182

South Asian (SAS) AF: 0.345 AC: 1662 AN: 4820

European-Finnish (FIN) AF: 0.448 AC: 4719 AN: 10534

Middle Eastern (MID) AF: 0.456 AC: 134 AN: 294

European-Non Finnish (NFE) AF: 0.469 AC: 31876 AN: 67968

Other (OTH) AF: 0.401 AC: 846 AN: 2108

Alfa AF: 0.442 Hom.: 28396

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
PhyloP100		-0.34
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: rs4299518; hg19: chr3-45809273;