NM_000341.4:c.1626G>C

Variant names:

• chr2-44320207-G-C
• rs886056071
• NM_000341.4:c.1626G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_000341.4(SLC3A1):​c.1626G>C​(p.Lys542Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC3A1 NM_000341.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.90

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]

PREPL (HGNC:30228): (prolyl endopeptidase like) The protein encoded by this gene belongs to the prolyl oligopeptidase subfamily of serine peptidases. Mutations in this gene have been associated with hypotonia-cystinuria syndrome, also known as the 2p21 deletion syndrome. Several alternatively spliced transcript variants encoding either the same or different isoforms have been described for this gene.[provided by RefSeq, Jan 2010]

ENSG00000285542 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2708898).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC3A1	NM_000341.4	c.1626G>C	p.Lys542Asn	missense_variant	Exon 10 of 10	ENST00000260649.11	NP_000332.2
PREPL	NM_001171613.2	c.*1149C>G		3_prime_UTR_variant	Exon 14 of 14	ENST00000409411.6	NP_001165084.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC3A1	ENST00000260649.11	c.1626G>C	p.Lys542Asn	missense_variant	Exon 10 of 10	1	NM_000341.4	ENSP00000260649.6
PREPL	ENST00000409411	c.*1149C>G		3_prime_UTR_variant	Exon 14 of 14	1	NM_001171613.2	ENSP00000387095.2
ENSG00000285542	ENST00000649044.1	n.*1637G>C		non_coding_transcript_exon_variant	Exon 15 of 15			ENSP00000497083.1
ENSG00000285542	ENST00000649044.1	n.*1637G>C		3_prime_UTR_variant	Exon 15 of 15			ENSP00000497083.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.033	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.45	T;.;.
Eigen	Benign	-0.053
Eigen_PC	Benign	0.019
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.54	T;T;T
M_CAP	Benign	0.062	D
MetaRNN	Benign	0.27	T;T;T
MetaSVM	Uncertain	0.024	D
MutationAssessor	Uncertain	2.1	M;.;.
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-2.3	N;N;N
REVEL	Uncertain	0.37
Sift	Benign	0.083	T;T;T
Sift4G	Uncertain	0.039	D;T;T
Polyphen		0.35	B;.;.
Vest4		0.028
MutPred		0.52		Loss of ubiquitination at K542 (P = 0.0092);.;.;
MVP		0.92
MPC		0.0062
ClinPred		0.55	D
GERP RS		2.3
Varity_R		0.14
gMVP		0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs886056071; hg19: chr2-44547346;