chr16-84041316-G-C

Variant names:

• chr16-84041316-G-C
• rs12716746
• NM_001080442.3:c.189+653C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001080442.3(SLC38A8):​c.189+653C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.798 in 152,330 control chromosomes in the GnomAD database, including 48,620 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 0.80 (48574 hom., cov: 33)
  • Exomes 𝑓: 0.86 (46 hom.)
• Consequence: SLC38A8 NM_001080442.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.159
• 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: PanelApp Australia, G2P, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics

ENSG00000285792 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.875 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.189+653C>G		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.189+653C>G		intron	N/A	ENSP00000299709.3	A6NNN8
	SLC38A8	ENST00000569816.1	TSL:4	c.-400C>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 3	ENSP00000455085.1	H3BP02
	SLC38A8	ENST00000569816.1	TSL:4	c.-400C>G		5_prime_UTR	Exon 1 of 3	ENSP00000455085.1	H3BP02

Frequencies

GnomAD3 genomes AF: 0.798 AC: 121321 AN: 152090 Hom.: 48511 Cov.: 33

Gnomad AFR AF: 0.810

Gnomad AMI AF: 0.879

Gnomad AMR AF: 0.772

Gnomad ASJ AF: 0.754

Gnomad EAS AF: 0.896

Gnomad SAS AF: 0.695

Gnomad FIN AF: 0.838

Gnomad MID AF: 0.756

Gnomad NFE AF: 0.790

Gnomad OTH AF: 0.804

GnomAD4 exome AF: 0.861 AC: 105 AN: 122 Hom.: 46 Cov.: 0 AF XY: 0.880 AC XY: 81 AN XY: 92

African (AFR) AF: 1.00 AC: 4 AN: 4

American (AMR) AF: 1.00 AC: 4 AN: 4

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 1.00 AC: 4 AN: 4

South Asian (SAS) AF: 1.00 AC: 2 AN: 2

European-Finnish (FIN) AF: 0.833 AC: 10 AN: 12

Middle Eastern (MID) AF: 1.00 AC: 2 AN: 2

European-Non Finnish (NFE) AF: 0.825 AC: 66 AN: 80

Other (OTH) AF: 0.929 AC: 13 AN: 14

GnomAD4 genome AF: 0.798 AC: 121447 AN: 152208 Hom.: 48574 Cov.: 33 AF XY: 0.798 AC XY: 59390 AN XY: 74426

African (AFR) AF: 0.811 AC: 33692 AN: 41546

American (AMR) AF: 0.772 AC: 11819 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.754 AC: 2616 AN: 3468

East Asian (EAS) AF: 0.896 AC: 4622 AN: 5156

South Asian (SAS) AF: 0.695 AC: 3347 AN: 4816

European-Finnish (FIN) AF: 0.838 AC: 8883 AN: 10602

Middle Eastern (MID) AF: 0.762 AC: 224 AN: 294

European-Non Finnish (NFE) AF: 0.790 AC: 53741 AN: 67996

Other (OTH) AF: 0.805 AC: 1701 AN: 2114

Alfa AF: 0.800 Hom.: 5689

Bravo AF: 0.794

Asia WGS AF: 0.812 AC: 2824 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.78
DANN	Benign	0.29
PhyloP100		-0.16
PromoterAI		0.0033	Neutral
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: rs12716746; hg19: chr16-84074921;