Variant 12-46769388-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_018018.5(SLC38A4):c.1340C>G(p.Pro447Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,188 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

SLC38A4
NM_018018.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.42

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.36230063).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC38A4	NM_018018.5 linkuse as main transcript	c.1340C>G	p.Pro447Arg	missense_variant	15/17	ENST00000266579.9	NP_060488.2	Q969I6A0A024R0X7
SLC38A4	NM_001143824.2 linkuse as main transcript	c.1340C>G	p.Pro447Arg	missense_variant	14/16		NP_001137296.1	Q969I6A0A024R0X7
SLC38A4	XM_005268997.3 linkuse as main transcript	c.1340C>G	p.Pro447Arg	missense_variant	14/16		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.1340C>G	p.Pro447Arg	missense_variant	15/17	1	NM_018018.5	ENSP00000266579.4		Q969I6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000797

AC:

AN:

251060

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135672

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461188

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726920

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000672

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

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.:

Bravo

AF:

0.00000378

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

Aug 12, 2022

The c.1340C>G (p.P447R) alteration is located in exon 15 (coding exon 13) of the SLC38A4 gene. This alteration results from a C to G substitution at nucleotide position 1340, causing the proline (P) at amino acid position 447 to be replaced by an arginine (R). 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

0.12

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.43

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

T;T

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.86

.;D

M_CAP

Benign

0.0098

MetaRNN

Benign

0.36

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

L;L

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-2.3

N;N

REVEL

Benign

0.16

Sift

Benign

0.11

T;T

Sift4G

Benign

0.14

T;T

Polyphen

0.60

P;P

Vest4

0.42

MutPred

0.51

Gain of catalytic residue at L442 (P = 2e-04);Gain of catalytic residue at L442 (P = 2e-04);

MVP

0.043

MPC

0.62

ClinPred

0.46

GERP RS

5.7

Varity_R

0.20

gMVP

0.49

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