rs3738985

Variant names:

• chr2-44275649-A-C
• rs3738985
• NM_000341.4:c.114A>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000341.4(SLC3A1):​c.114A>C​(p.Gly38Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.767 in 1,613,626 control chromosomes in the GnomAD database, including 480,440 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. G38G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.75 (43627 hom., cov: 33)
  • Exomes 𝑓: 0.77 (436813 hom.)
• Consequence: SLC3A1 NM_000341.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 0.0880
• Publications: 33 publications found

Genes affected

SLC3A1 (HGNC:11025): (solute carrier family 3 member 1) This gene encodes a type II membrane glycoprotein which is one of the components of the renal amino acid transporter which transports neutral and basic amino acids in the renal tubule and intestinal tract. Mutations and deletions in this gene are associated with cystinuria. Alternatively spliced transcript variants have been described, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

SLC3A1 Gene-Disease associations (from GenCC):

• cystinuria

  Inheritance: AR, AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics, PanelApp Australia
• cystinuria type A

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000285542 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BP6: Variant 2-44275649-A-C is Benign according to our data. Variant chr2-44275649-A-C is described in ClinVar as Benign. ClinVar VariationId is 336184.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.088 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.817 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000341.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC3A1	NM_000341.4	MANE Select	c.114A>C	p.Gly38Gly	synonymous	Exon 1 of 10	NP_000332.2	Q07837-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC3A1	ENST00000260649.11	TSL:1 MANE Select	c.114A>C	p.Gly38Gly	synonymous	Exon 1 of 10	ENSP00000260649.6	Q07837-1
	SLC3A1	ENST00000409229.7	TSL:1	c.114A>C	p.Gly38Gly	synonymous	Exon 1 of 9	ENSP00000386620.3	Q07837-6
	SLC3A1	ENST00000409387.5	TSL:1	c.114A>C	p.Gly38Gly	synonymous	Exon 1 of 10	ENSP00000387308.1	B8ZZK1

Frequencies

GnomAD3 genomes AF: 0.752 AC: 114387 AN: 152090 Hom.: 43579 Cov.: 33

Gnomad AFR AF: 0.795

Gnomad AMI AF: 0.706

Gnomad AMR AF: 0.688

Gnomad ASJ AF: 0.799

Gnomad EAS AF: 0.356

Gnomad SAS AF: 0.838

Gnomad FIN AF: 0.672

Gnomad MID AF: 0.813

Gnomad NFE AF: 0.775

Gnomad OTH AF: 0.749

GnomAD2 exomes AF: 0.723 AC: 181054 AN: 250552 AF XY: 0.735

Gnomad AFR exome AF: 0.789

Gnomad AMR exome AF: 0.600

Gnomad ASJ exome AF: 0.789

Gnomad EAS exome AF: 0.355

Gnomad FIN exome AF: 0.679

Gnomad NFE exome AF: 0.776

Gnomad OTH exome AF: 0.745

GnomAD4 exome AF: 0.769 AC: 1123652 AN: 1461418 Hom.: 436813 Cov.: 61 AF XY: 0.772 AC XY: 560974 AN XY: 726974

African (AFR) AF: 0.802 AC: 26858 AN: 33468

American (AMR) AF: 0.610 AC: 27227 AN: 44622

Ashkenazi Jewish (ASJ) AF: 0.795 AC: 20768 AN: 26134

East Asian (EAS) AF: 0.397 AC: 15770 AN: 39688

South Asian (SAS) AF: 0.854 AC: 73626 AN: 86236

European-Finnish (FIN) AF: 0.684 AC: 36512 AN: 53404

Middle Eastern (MID) AF: 0.838 AC: 4832 AN: 5768

European-Non Finnish (NFE) AF: 0.785 AC: 872168 AN: 1111722

Other (OTH) AF: 0.760 AC: 45891 AN: 60376

GnomAD4 genome AF: 0.752 AC: 114494 AN: 152208 Hom.: 43627 Cov.: 33 AF XY: 0.746 AC XY: 55476 AN XY: 74414

African (AFR) AF: 0.796 AC: 33042 AN: 41536

American (AMR) AF: 0.688 AC: 10512 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.799 AC: 2774 AN: 3470

East Asian (EAS) AF: 0.355 AC: 1837 AN: 5168

South Asian (SAS) AF: 0.839 AC: 4050 AN: 4830

European-Finnish (FIN) AF: 0.672 AC: 7126 AN: 10602

Middle Eastern (MID) AF: 0.816 AC: 240 AN: 294

European-Non Finnish (NFE) AF: 0.775 AC: 52685 AN: 68000

Other (OTH) AF: 0.751 AC: 1587 AN: 2114

Alfa AF: 0.767 Hom.: 148471

Bravo AF: 0.747

Asia WGS AF: 0.642 AC: 2236 AN: 3478

EpiCase AF: 0.786

EpiControl AF: 0.782

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	Cystinuria (4)
-	-	2	not provided (2)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.2
DANN	Benign	0.31
PhyloP100		0.088
PromoterAI		-0.016	Neutral
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: rs3738985; hg19: chr2-44502788; COSMIC: COSV53222180; COSMIC: COSV53222180;