chr2-44275696-C-A

Position:

• chr2-44275696-C-A

Variant summary

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

The NM_000341.4(SLC3A1):​c.161C>A​(p.Ser54Tyr) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC3A1 NM_000341.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.326

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 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=0.1363225).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC3A1	NM_000341.4	c.161C>A	p.Ser54Tyr	missense_variant	1/10	ENST00000260649.11
SLC3A1	XM_011533047.4	c.161C>A	p.Ser54Tyr	missense_variant	1/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC3A1	ENST00000260649.11	c.161C>A	p.Ser54Tyr	missense_variant	1/10	1	NM_000341.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 02, 2023

The c.161C>A (p.S54Y) alteration is located in exon 1 (coding exon 1) of the SLC3A1 gene. This alteration results from a C to A substitution at nucleotide position 161, causing the serine (S) at amino acid position 54 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Uncertain	0.039	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	15
DANN	Benign	0.85
DEOGEN2	Benign	0.021	T;T;T;.;.;.
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.61	T;T;T;T;T;T
M_CAP	Uncertain	0.099	D
MetaRNN	Benign	0.14	T;T;T;T;T;T
MetaSVM	Uncertain	0.76	D
MutationAssessor	Benign	0.69	.;N;.;N;N;N
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.2	.;N;N;N;N;N
REVEL	Uncertain	0.35
Sift	Uncertain	0.019	.;D;D;D;D;D
Sift4G	Uncertain	0.031	D;D;D;D;D;D
Polyphen		0.033, 0.058	.;B;B;.;.;.
Vest4		0.29
MutPred		0.39		Loss of disorder (P = 0.0055);Loss of disorder (P = 0.0055);Loss of disorder (P = 0.0055);Loss of disorder (P = 0.0055);Loss of disorder (P = 0.0055);Loss of disorder (P = 0.0055);
MVP		0.75
MPC		0.0074
ClinPred		0.15	T
GERP RS		3.7
Varity_R		0.090
gMVP		0.35

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-44502835;