dbSNP rs4782578: SLC38A8:c.633-264C>T (chr16-84029815-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001080442.3(SLC38A8):c.633-264C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 152,124 control chromosomes in the GnomAD database, including 6,261 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6261 hom., cov: 33)

Consequence

SLC38A8
NM_001080442.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.89

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 16-84029815-G-A is Benign according to our data. Variant chr16-84029815-G-A is described in ClinVar as Benign. ClinVar VariationId is 1238038.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.397 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC38A8	NM_001080442.3 link	c.633-264C>T		intron_variant	Intron 5 of 10	ENST00000299709.8	NP_001073911.1	A6NNN8
SLC38A8	XM_017022946.1 link	c.633-264C>T		intron_variant	Intron 6 of 11		XP_016878435.1	A6NNN8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC38A8	ENST00000299709.8 link	c.633-264C>T		intron_variant	Intron 5 of 10	5	NM_001080442.3	ENSP00000299709.3		A6NNN8
SLC38A8	ENST00000568178.1 link	c.633-264C>T		intron_variant	Intron 5 of 6	5		ENSP00000457737.1		H3BUP5

Frequencies

GnomAD3 genomes

AF:

0.282

AC:

42931

AN:

152006

Hom.:

6254

Cov.:

show subpopulations

Gnomad AFR

AF:

0.327

Gnomad AMI

AF:

0.204

Gnomad AMR

AF:

0.272

Gnomad ASJ

AF:

0.251

Gnomad EAS

AF:

0.412

Gnomad SAS

AF:

0.232

Gnomad FIN

AF:

0.280

Gnomad MID

AF:

0.275

Gnomad NFE

AF:

0.255

Gnomad OTH

AF:

0.271

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.282

AC:

42969

AN:

152124

Hom.:

6261

Cov.:

AF XY:

0.284

AC XY:

21135

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.327

AC:

13575

AN:

41492

American (AMR)

AF:

0.273

AC:

4166

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.251

AC:

871

AN:

3470

East Asian (EAS)

AF:

0.411

AC:

2127

AN:

5172

South Asian (SAS)

AF:

0.232

AC:

1116

AN:

4820

European-Finnish (FIN)

AF:

0.280

AC:

2961

AN:

10590

Middle Eastern (MID)

AF:

0.269

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.255

AC:

17321

AN:

67992

Other (OTH)

AF:

0.269

AC:

567

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1574

3147

4721

6294

7868

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

450

900

1350

1800

2250

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.270

Hom.:

9005

Bravo

AF:

0.288

Asia WGS

AF:

0.344

AC:

1197

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 19, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.12

(source)

DANN

Benign

0.50

PhyloP100

-1.9

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over