Variant 14-61046125-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_153811.3(SLC38A6):c.883A>G(p.Ile295Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,458,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 0.0000014 ( 0 hom. )

Consequence

SLC38A6
NM_153811.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.209

Variant links:

Genes affected

SLC38A6 (HGNC:19863): (solute carrier family 38 member 6) Predicted to enable L-glutamine transmembrane transporter activity. Predicted to be involved in amino acid transmembrane transport and glutamine transport. Predicted to be located in plasma membrane. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC38A6 links:

LOC101927756 (HGNC:):

LOC101927756 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=0.07729152).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC38A6	NM_153811.3 linkuse as main transcript	c.883A>G	p.Ile295Val	missense_variant	12/16	ENST00000267488.9
LOC101927756	XR_943921.2 linkuse as main transcript	n.89-589T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC38A6	ENST00000267488.9 linkuse as main transcript	c.883A>G	p.Ile295Val	missense_variant	12/16	1	NM_153811.3	P1	Q8IZM9-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250510

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135420

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000328

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1458882

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725846

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 28, 2023

The c.883A>G (p.I295V) alteration is located in exon 12 (coding exon 12) of the SLC38A6 gene. This alteration results from a A to G substitution at nucleotide position 883, causing the isoleucine (I) at amino acid position 295 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

0.10

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.61

CADD

Benign

5.1

DANN

Uncertain

0.98

DEOGEN2

Benign

0.070

.;T;T;.

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.54

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.71

T;T;T;T

M_CAP

Benign

0.0039

MetaRNN

Benign

0.077

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.60

N;N;.;.

MutationTaster

Benign

0.52

N;N;N

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.27

N;N;N;N

REVEL

Benign

0.043

Sift

Benign

0.17

T;T;T;T

Sift4G

Benign

0.10

T;T;T;T

Polyphen

0.0010

B;B;.;.

Vest4

0.25

MVP

0.030

MPC

0.017

ClinPred

0.075

GERP RS

1.4

Varity_R

0.050

gMVP

0.18

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