chr2-44275635-A-C

Variant names:

• chr2-44275635-A-C
• rs748553507
• NM_000341.4:c.100A>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000341.4(SLC3A1):​c.100A>C​(p.Thr34Pro) 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. 14/21 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: 31)
• Consequence: SLC3A1 NM_000341.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.51

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]

ENSG00000285542 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.090911984).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC3A1	NM_000341.4	c.100A>C	p.Thr34Pro	missense_variant	Exon 1 of 10	ENST00000260649.11	NP_000332.2
SLC3A1	XM_011533047.4	c.100A>C	p.Thr34Pro	missense_variant	Exon 1 of 10		XP_011531349.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC3A1	ENST00000260649.11	c.100A>C	p.Thr34Pro	missense_variant	Exon 1 of 10	1	NM_000341.4	ENSP00000260649.6
ENSG00000285542	ENST00000649044.1	n.*111A>C		non_coding_transcript_exon_variant	Exon 6 of 15			ENSP00000497083.1
ENSG00000285542	ENST00000649044.1	n.*111A>C		3_prime_UTR_variant	Exon 6 of 15			ENSP00000497083.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Uncertain	0.043	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	9.0
DANN	Benign	0.62
DEOGEN2	Benign	0.011	T;T;T;.;.;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.48	T;T;T;T;T;T
M_CAP	Benign	0.063	D
MetaRNN	Benign	0.091	T;T;T;T;T;T
MetaSVM	Pathogenic	0.90	D
MutationAssessor	Benign	0.0	.;N;.;N;N;N
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.59	.;N;N;N;N;N
REVEL	Uncertain	0.42
Sift	Benign	0.15	.;T;T;T;T;T
Sift4G	Benign	0.089	T;T;T;T;T;T
Polyphen		0.17, 0.11	.;B;B;.;.;.
Vest4		0.13
MutPred		0.22		Gain of catalytic residue at T34 (P = 6e-04);Gain of catalytic residue at T34 (P = 6e-04);Gain of catalytic residue at T34 (P = 6e-04);Gain of catalytic residue at T34 (P = 6e-04);Gain of catalytic residue at T34 (P = 6e-04);Gain of catalytic residue at T34 (P = 6e-04);
MVP		0.63
MPC		0.0059
ClinPred		0.046	T
GERP RS		1.6
Varity_R		0.095
gMVP		0.28

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: rs748553507; hg19: chr2-44502774;