chr16-84013110-A-G

Position:

• chr16-84013110-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0240

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 -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/exons	MANE	UniProt
SLC38A8	NM_001080442.3	c.1163-58T>C		intron_variant		ENST00000299709.8
SLC38A8	XM_017022946.1	c.1163-58T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC38A8	ENST00000299709.8	c.1163-58T>C		intron_variant		5	NM_001080442.3	P1
SLC38A8	ENST00000568003.1	n.239-58T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.171 AC: 25972 AN: 152090 Hom.: 2921 Cov.: 33

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

Gnomad4 AFR exome AF: 0.331

Gnomad4 AMR exome AF: 0.162

Gnomad4 ASJ exome AF: 0.130

Gnomad4 EAS exome AF: 0.0663

Gnomad4 SAS exome AF: 0.140

Gnomad4 FIN exome AF: 0.101

Gnomad4 NFE exome AF: 0.105

Gnomad4 OTH exome AF: 0.125

GnomAD4 genome AF: 0.171 AC: 26011 AN: 152208 Hom.: 2928 Cov.: 33 AF XY: 0.169 AC XY: 12583 AN XY: 74430

Gnomad4 AFR AF: 0.327

Gnomad4 AMR AF: 0.145

Gnomad4 ASJ AF: 0.129

Gnomad4 EAS AF: 0.0692

Gnomad4 SAS AF: 0.145

Gnomad4 FIN AF: 0.0980

Gnomad4 NFE AF: 0.104

Gnomad4 OTH AF: 0.152

Alfa AF: 0.119 Hom.: 1869

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
DANN	Benign	0.63

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: rs11864146; hg19: chr16-84046715; COSMIC: COSV55309802;