Variant 12-46778571-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_018018.5(SLC38A4):c.923A>G(p.Asp308Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,612,960 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

SLC38A4
NM_018018.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.156

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.013355374).

BP6

Variant 12-46778571-T-C is Benign according to our data. Variant chr12-46778571-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2470960.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC38A4	NM_018018.5 linkuse as main transcript	c.923A>G	p.Asp308Gly	missense_variant	11/17	ENST00000266579.9	NP_060488.2	Q969I6A0A024R0X7
SLC38A4	NM_001143824.2 linkuse as main transcript	c.923A>G	p.Asp308Gly	missense_variant	10/16		NP_001137296.1	Q969I6A0A024R0X7
SLC38A4	XM_005268997.3 linkuse as main transcript	c.923A>G	p.Asp308Gly	missense_variant	10/16		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.923A>G	p.Asp308Gly	missense_variant	11/17	1	NM_018018.5	ENSP00000266579.4		Q969I6

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

151996

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000776

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000760

AC:

AN:

249990

Hom.:

AF XY:

0.0000740

AC XY:

AN XY:

135078

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00104

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:

0.00000958

AC:

AN:

1460964

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

726808

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000353

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

AF:

0.0000263

AC:

AN:

151996

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74230

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000776

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000302

ExAC

AF:

0.0000577

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 27, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.74

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.012

T;T

Eigen

Benign

-0.81

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.0053

LIST_S2

Benign

0.49

.;T

M_CAP

Benign

0.0046

MetaRNN

Benign

0.013

T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.34

N;N

PrimateAI

Benign

0.21

PROVEAN

Benign

-0.14

N;N

REVEL

Benign

0.015

Sift

Benign

0.41

T;T

Sift4G

Benign

0.51

T;T

Polyphen

0.0

B;B

Vest4

0.21

MutPred

0.36

Gain of catalytic residue at D308 (P = 6e-04);Gain of catalytic residue at D308 (P = 6e-04);

MVP

0.043

MPC

0.34

ClinPred

0.0066

GERP RS

1.4

Varity_R

0.056

gMVP

0.38

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