16-84013110-A-G

Variant names:

• chr16-84013110-A-G
• rs11864146
• NM_001080442.3:c.1163-58T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 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: PanelApp Australia, G2P, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics

ACMG classification

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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC38A8	NM_001080442.3	MANE Select	c.1163-58T>C		intron	N/A	NP_001073911.1	A6NNN8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC38A8	ENST00000299709.8	TSL:5 MANE Select	c.1163-58T>C		intron	N/A	ENSP00000299709.3	A6NNN8
	SLC38A8	ENST00000912183.1		c.1163-58T>C		intron	N/A	ENSP00000582242.1
	SLC38A8	ENST00000946738.1		c.1163-58T>C		intron	N/A	ENSP00000616797.1

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

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

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

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: 48 AN: 294

European-Non Finnish (NFE) AF: 0.104 AC: 7088 AN: 68008

Other (OTH) AF: 0.152 AC: 321 AN: 2116

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.5
DANN	Benign	0.63
PhyloP100		-0.024
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: rs11864146; hg19: chr16-84046715; COSMIC: COSV55309802;