2-44275701-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_000341.4(SLC3A1):c.166G>A(p.Glu56Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,828 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: SLC3A1 NM_000341.4 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 3.26

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.19505551).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC3A1	NM_000341.4	c.166G>A	p.Glu56Lys	missense_variant	1/10	ENST00000260649.11
SLC3A1	XM_011533047.4	c.166G>A	p.Glu56Lys	missense_variant	1/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC3A1	ENST00000260649.11	c.166G>A	p.Glu56Lys	missense_variant	1/10	1	NM_000341.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000547 AC: 8 AN: 1461828 Hom.: 0 Cov.: 35 AF XY: 0.00000688 AC XY: 5 AN XY: 727222

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000719

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Cystinuria Uncertain:2

Uncertain significance, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Apr 21, 2022	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Uncertain	0.057	T
BayesDel_noAF	Benign	-0.16
Cadd	Benign	14
Dann	Uncertain	0.99
DEOGEN2	Benign	0.014	T;T;T;.;.;.
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.65	T;T;T;T;T;T
M_CAP	Benign	0.049	D
MetaRNN	Benign	0.20	T;T;T;T;T;T
MetaSVM	Uncertain	0.69	D
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.31	T
Sift4G	Benign	0.21	T;T;T;T;T;T
Polyphen		0.0020, 0.0030	.;B;B;.;.;.
Vest4		0.25
MutPred		0.33		Gain of methylation at E56 (P = 0.0071);Gain of methylation at E56 (P = 0.0071);Gain of methylation at E56 (P = 0.0071);Gain of methylation at E56 (P = 0.0071);Gain of methylation at E56 (P = 0.0071);Gain of methylation at E56 (P = 0.0071);
MVP		0.89
MPC		0.0063
ClinPred		0.44	T
GERP RS		4.8
Varity_R		0.18
gMVP		0.42

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: rs886056067; hg19: chr2-44502840; COSMIC: COSV105021408; COSMIC: COSV105021408;