16-84009787-G-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001080442.3(SLC38A8):c.1305C>G(p.Phe435Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000385 in 1,613,672 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0019 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00023 ( 2 hom. )

Consequence

SLC38A8
NM_001080442.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.935

Variant links:

Genes affected

SLC38A8 (HGNC:32434): (solute carrier family 38 member 8) This gene encodes a putative sodium-dependent amino-acid/proton antiporter. The protein has eleven transmembrane domains, an extracellular N-terminus and an intracellular C-terminal tail. The protein is a member of the SLC38 sodium-coupled neutral amino acid transporter family of proteins. Mutations in this gene result in foveal hypoplasia with or without optic nerve misrouting and/or anterior segment dysgenesis. [provided by RefSeq, May 2014]

SLC38A8 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0053940117).

BP6

Variant 16-84009787-G-C is Benign according to our data. Variant chr16-84009787-G-C is described in ClinVar as [Benign]. Clinvar id is 1601693.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-84009787-G-C is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00185 (282/152300) while in subpopulation AFR AF= 0.0065 (270/41570). AF 95% confidence interval is 0.00586. There are 0 homozygotes in gnomad4. There are 137 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC38A8	NM_001080442.3 link	c.1305C>G	p.Phe435Leu	missense_variant	Exon 11 of 11	ENST00000299709.8	NP_001073911.1	A6NNN8
SLC38A8	XM_017022946.1 link	c.1305C>G	p.Phe435Leu	missense_variant	Exon 12 of 12		XP_016878435.1	A6NNN8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC38A8	ENST00000299709.8 link	c.1305C>G	p.Phe435Leu	missense_variant	Exon 11 of 11	5	NM_001080442.3	ENSP00000299709.3		A6NNN8
SLC38A8	ENST00000568003.1 link	n.381C>G		non_coding_transcript_exon_variant	Exon 3 of 3	3

Frequencies

GnomAD3 genomes

AF:

0.00183

AC:

279

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00644

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.000507

AC:

127

AN:

250646

Hom.:

AF XY:

0.000354

AC XY:

AN XY:

135534

show subpopulations

Gnomad AFR exome

AF:

0.00680

Gnomad AMR exome

AF:

0.000261

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000981

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.000491

GnomAD4 exome

AF:

0.000232

AC:

339

AN:

1461372

Hom.:

Cov.:

AF XY:

0.000230

AC XY:

167

AN XY:

726964

show subpopulations

Gnomad4 AFR exome

AF:

0.00777

Gnomad4 AMR exome

AF:

0.000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000928

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000810

Gnomad4 OTH exome

AF:

0.000696

GnomAD4 genome

AF:

0.00185

AC:

282

AN:

152300

Hom.:

Cov.:

AF XY:

0.00184

AC XY:

137

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.00650

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.000268

Hom.:

Bravo

AF:

0.00190

ESP6500AA

AF:

0.00614

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000766

AC:

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Oct 14, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

SLC38A8-related disorder

Benign:1

Aug 15, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.46

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.80

DANN

Benign

0.32

DEOGEN2

Benign

0.012

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.39

MetaRNN

Benign

0.0054

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-0.63

PrimateAI

Benign

0.38

PROVEAN

Benign

1.4

REVEL

Benign

0.017

Sift

Benign

0.54

Polyphen

0.0

Vest4

0.12

MutPred

0.30

Gain of disorder (P = 0.1789);

MVP

0.030

ClinPred

0.0067

GERP RS

-0.69

Varity_R

0.036

gMVP

0.77

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