Genetic Variant SLC38A8:c.189+653C>G (chr16-84041316-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001080442.3(SLC38A8):c.189+653C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.798 in 152,330 control chromosomes in the GnomAD database, including 48,620 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.80 ( 48574 hom., cov: 33)

Exomes 𝑓: 0.86 ( 46 hom. )

Consequence

SLC38A8
NM_001080442.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.159

Publications

3 publications found

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 Gene-Disease associations (from GenCC):

foveal hypoplasia - optic nerve decussation defect - anterior segment dysgenesis syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics

SLC38A8 links:

ENSG00000285792 (HGNC:):

ENSG00000285792 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.02).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.875 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC38A8	NM_001080442.3 link	c.189+653C>G		intron_variant	Intron 2 of 10	ENST00000299709.8	NP_001073911.1	A6NNN8
SLC38A8	XM_017022946.1 link	c.189+653C>G		intron_variant	Intron 3 of 11		XP_016878435.1	A6NNN8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC38A8	ENST00000299709.8 link	c.189+653C>G		intron_variant	Intron 2 of 10	5	NM_001080442.3	ENSP00000299709.3		A6NNN8

Frequencies

GnomAD3 genomes

AF:

0.798

AC:

121321

AN:

152090

Hom.:

48511

Cov.:

show subpopulations

Gnomad AFR

AF:

0.810

Gnomad AMI

AF:

0.879

Gnomad AMR

AF:

0.772

Gnomad ASJ

AF:

0.754

Gnomad EAS

AF:

0.896

Gnomad SAS

AF:

0.695

Gnomad FIN

AF:

0.838

Gnomad MID

AF:

0.756

Gnomad NFE

AF:

0.790

Gnomad OTH

AF:

0.804

GnomAD4 exome

AF:

0.861

AC:

105

AN:

122

Hom.:

Cov.:

AF XY:

0.880

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

1.00

AC:

AN:

American (AMR)

AF:

1.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AF:

1.00

AC:

AN:

European-Finnish (FIN)

AF:

0.833

AC:

AN:

Middle Eastern (MID)

AF:

1.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.825

AC:

AN:

Other (OTH)

AF:

0.929

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.544

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.798

AC:

121447

AN:

152208

Hom.:

48574

Cov.:

AF XY:

0.798

AC XY:

59390

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.811

AC:

33692

AN:

41546

American (AMR)

AF:

0.772

AC:

11819

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.754

AC:

2616

AN:

3468

East Asian (EAS)

AF:

0.896

AC:

4622

AN:

5156

South Asian (SAS)

AF:

0.695

AC:

3347

AN:

4816

European-Finnish (FIN)

AF:

0.838

AC:

8883

AN:

10602

Middle Eastern (MID)

AF:

0.762

AC:

224

AN:

294

European-Non Finnish (NFE)

AF:

0.790

AC:

53741

AN:

67996

Other (OTH)

AF:

0.805

AC:

1701

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1292

2584

3875

5167

6459

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.800

Hom.:

5689

Bravo

AF:

0.794

Asia WGS

AF:

0.812

AC:

2824

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.78

(source)

DANN

Benign

0.29

PhyloP100

-0.16

PromoterAI

0.0033

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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16-84041316-G-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over