Genetic Variant SLC38A8:c.1163-58T>C (chr16-84013110-A-G) – 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.1163-58T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 1,605,078 control chromosomes in the GnomAD database, including 13,591 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 0.17 ( 2928 hom., cov: 33)

Exomes 𝑓: 0.11 ( 10663 hom. )

Consequence

SLC38A8
NM_001080442.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0240

Publications

9 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:

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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=-0.91).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC38A8	NM_001080442.3 link	c.1163-58T>C		intron_variant	Intron 9 of 10	ENST00000299709.8	NP_001073911.1	A6NNN8
SLC38A8	XM_017022946.1 link	c.1163-58T>C		intron_variant	Intron 10 of 11		XP_016878435.1	A6NNN8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC38A8	ENST00000299709.8 link	c.1163-58T>C		intron_variant	Intron 9 of 10	5	NM_001080442.3	ENSP00000299709.3		A6NNN8
SLC38A8	ENST00000568003.1 link	n.239-58T>C		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes

AF:

0.171

AC:

25972

AN:

152090

Hom.:

2921

Cov.:

show subpopulations

Gnomad AFR

AF:

0.327

Gnomad AMI

AF:

0.240

Gnomad AMR

AF:

0.145

Gnomad ASJ

AF:

0.129

Gnomad EAS

AF:

0.0692

Gnomad SAS

AF:

0.145

Gnomad FIN

AF:

0.0980

Gnomad MID

AF:

0.158

Gnomad NFE

AF:

0.104

Gnomad OTH

AF:

0.153

GnomAD4 exome

AF:

0.114

AC:

165663

AN:

1452870

Hom.:

10663

AF XY:

0.113

AC XY:

82062

AN XY:

723130

show subpopulations

African (AFR)

AF:

0.331

AC:

10984

AN:

33218

American (AMR)

AF:

0.162

AC:

7142

AN:

43980

Ashkenazi Jewish (ASJ)

AF:

0.130

AC:

3359

AN:

25746

East Asian (EAS)

AF:

0.0663

AC:

2627

AN:

39638

South Asian (SAS)

AF:

0.140

AC:

11968

AN:

85658

European-Finnish (FIN)

AF:

0.101

AC:

5367

AN:

53134

Middle Eastern (MID)

AF:

0.147

AC:

834

AN:

5690

European-Non Finnish (NFE)

AF:

0.105

AC:

115875

AN:

1105814

Other (OTH)

AF:

0.125

AC:

7507

AN:

59992

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

7145

14290

21434

28579

35724

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.171

AC:

26011

AN:

152208

Hom.:

2928

Cov.:

AF XY:

0.169

AC XY:

12583

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.327

AC:

13577

AN:

41500

American (AMR)

AF:

0.145

AC:

2211

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.129

AC:

448

AN:

3472

East Asian (EAS)

AF:

0.0692

AC:

357

AN:

5162

South Asian (SAS)

AF:

0.145

AC:

701

AN:

4826

European-Finnish (FIN)

AF:

0.0980

AC:

1041

AN:

10622

Middle Eastern (MID)

AF:

0.163

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.104

AC:

7088

AN:

68008

Other (OTH)

AF:

0.152

AC:

321

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1054

2107

3161

4214

5268

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.128

Hom.:

5641

Bravo

AF:

0.183

Asia WGS

AF:

0.120

AC:

418

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.5

(source)

DANN

Benign

0.63

PhyloP100

-0.024

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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chr16-84013110-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

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