Variant 12-46788529-T-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_018018.5(SLC38A4):c.209A>T(p.His70Leu) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000000685 in 1,460,046 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SLC38A4
NM_018018.5 missense, splice_region

Scores

Splicing: ADA: 0.9845

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.32

Variant links:

Genes affected

SLC38A4 (HGNC:14679): (solute carrier family 38 member 4) SLC38A4 is found predominantly in liver and transports both cationic and neutral amino acids. The transport of cationic amino acids by SLC38A4 is Na(+) and pH independent, while the transport of neutral amino acids is Na(+) and pH dependent (Hatanaka et al., 2001 [PubMed 11342143]).[supplied by OMIM, Mar 2008]

SLC38A4 links:

SLC38A4-AS1 (HGNC:):

SLC38A4-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC38A4	NM_018018.5 linkuse as main transcript	c.209A>T	p.His70Leu	missense_variant, splice_region_variant	4/17	ENST00000266579.9	NP_060488.2	Q969I6A0A024R0X7
SLC38A4	NM_001143824.2 linkuse as main transcript	c.209A>T	p.His70Leu	missense_variant, splice_region_variant	3/16		NP_001137296.1	Q969I6A0A024R0X7
SLC38A4	XM_005268997.3 linkuse as main transcript	c.209A>T	p.His70Leu	missense_variant, splice_region_variant	3/16		XP_005269054.1	Q969I6A0A024R0X7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC38A4	ENST00000266579.9 linkuse as main transcript	c.209A>T	p.His70Leu	missense_variant, splice_region_variant	4/17	1	NM_018018.5	ENSP00000266579.4		Q969I6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460046

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726356

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Sep 22, 2023

The c.209A>T (p.H70L) alteration is located in exon 4 (coding exon 2) of the SLC38A4 gene. This alteration results from a A to T substitution at nucleotide position 209, causing the histidine (H) at amino acid position 70 to be replaced by a leucine (L). 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

0.093

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Uncertain

DANN

Benign

0.97

DEOGEN2

Benign

0.043

T;T;T;.

Eigen

Benign

-0.0055

Eigen_PC

Benign

0.17

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.86

.;D;D;D

M_CAP

Benign

0.012

MetaRNN

Benign

0.18

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;N;.;.

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-1.3

N;N;N;N

REVEL

Benign

0.12

Sift

Benign

0.46

T;T;T;T

Sift4G

Benign

0.51

T;T;.;.

Polyphen

0.079

B;B;.;.

Vest4

0.32

MutPred

0.38

Gain of catalytic residue at T74 (P = 0.0478);Gain of catalytic residue at T74 (P = 0.0478);Gain of catalytic residue at T74 (P = 0.0478);Gain of catalytic residue at T74 (P = 0.0478);

MVP

0.068

MPC

0.34

ClinPred

0.65

GERP RS

5.5

Varity_R

0.19

gMVP

0.39

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.98

dbscSNV1_RF

Pathogenic

0.87

SpliceAI score (max)

0.080

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over