16-84029815-G-A

Variant names:

• chr16-84029815-G-A
• rs4782578
• NM_001080442.3:c.633-264C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.89
• Publications: 3 publications found

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

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080442.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC38A8	NM_001080442.3	MANE Select	c.633-264C>T		intron	N/A	NP_001073911.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC38A8	ENST00000299709.8	TSL:5 MANE Select	c.633-264C>T		intron	N/A	ENSP00000299709.3
	SLC38A8	ENST00000568178.1	TSL:5	c.633-264C>T		intron	N/A	ENSP00000457737.1

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42931 AN: 152006 Hom.: 6254 Cov.: 33

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.: 33 AF XY: 0.284 AC XY: 21135 AN XY: 74362

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: 79 AN: 294

European-Non Finnish (NFE) AF: 0.255 AC: 17321 AN: 67992

Other (OTH) AF: 0.269 AC: 567 AN: 2110

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

Submissions by phenotype

not provided Benign:2

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.12
DANN	Benign	0.50
PhyloP100		-1.9
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4782578; hg19: chr16-84063420;