Genetic Variant SLC7A2:p.Met37Val (chr8-17543448-A-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001370338.1(SLC7A2):c.109A>G(p.Met37Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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: 0.0000068 ( 0 hom. )

Consequence

SLC7A2
NM_001370338.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0770

Variant links:

Genes affected

SLC7A2 (HGNC:11060): (solute carrier family 7 member 2) The protein encoded by this gene is a cationic amino acid transporter and a member of the APC (amino acid-polyamine-organocation) family of transporters. The encoded membrane protein is responsible for the cellular uptake of arginine, lysine and ornithine. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

SLC7A2 links:

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ACMG classification

Classification made for transcript

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=0.11821324).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC7A2	NM_001370338.1 link	c.109A>G	p.Met37Val	missense_variant	Exon 3 of 13	ENST00000494857.6	NP_001357267.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC7A2	ENST00000494857.6 link	c.109A>G	p.Met37Val	missense_variant	Exon 3 of 13	5	NM_001370338.1	ENSP00000419140.2		P52569-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000684

AC:

AN:

1461892

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727248

show subpopulations

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:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000629

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 03, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.229A>G (p.M77V) alteration is located in exon 2 (coding exon 2) of the SLC7A2 gene. This alteration results from a A to G substitution at nucleotide position 229, causing the methionine (M) at amino acid position 77 to be replaced by a valine (V). 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

0.047

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.33

T;T;.;.;.;.

Eigen

Benign

-0.86

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.76

.;T;.;T;T;T

M_CAP

Benign

0.024

MetaRNN

Benign

0.12

T;T;T;T;T;T

MetaSVM

Benign

-0.77

MutationAssessor

Benign

-1.1

N;N;.;.;.;.

PrimateAI

Benign

0.40

PROVEAN

Benign

-1.1

N;N;N;N;N;.

REVEL

Benign

0.25

Sift

Benign

0.12

T;T;T;T;T;.

Sift4G

Benign

0.27

T;T;T;T;T;.

Polyphen

0.0

B;B;B;B;B;.

Vest4

0.087

MutPred

0.58

Loss of stability (P = 0.035);Loss of stability (P = 0.035);.;.;.;.;

MVP

0.52

MPC

0.021

ClinPred

0.13

GERP RS

1.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.038

gMVP

0.24

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over