rs4782578

Positions:

• chr16-84029815-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
SLC38A8	NM_001080442.3	c.633-264C>T		intron_variant		ENST00000299709.8	NP_001073911.1
SLC38A8	XM_017022946.1	c.633-264C>T		intron_variant			XP_016878435.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC38A8	ENST00000299709.8	c.633-264C>T		intron_variant		5	NM_001080442.3	ENSP00000299709	P1
SLC38A8	ENST00000568178.1	c.633-264C>T		intron_variant		5		ENSP00000457737

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

Gnomad4 AFR AF: 0.327

Gnomad4 AMR AF: 0.273

Gnomad4 ASJ AF: 0.251

Gnomad4 EAS AF: 0.411

Gnomad4 SAS AF: 0.232

Gnomad4 FIN AF: 0.280

Gnomad4 NFE AF: 0.255

Gnomad4 OTH AF: 0.269

Alfa AF: 0.264 Hom.: 5554

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.12
DANN	Benign	0.50

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

Other links and lift over

dbSNP: rs4782578; hg19: chr16-84063420;