16-84041316-G-C

Position:

• chr16-84041316-G-C

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC38A8	NM_001080442.3	c.189+653C>G		intron_variant		ENST00000299709.8
SLC38A8	XM_017022946.1	c.189+653C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC38A8	ENST00000299709.8	c.189+653C>G		intron_variant		5	NM_001080442.3	P1
	ENST00000647688.1	n.527G>C		non_coding_transcript_exon_variant	1/2
SLC38A8	ENST00000569816.1	c.-400C>G		5_prime_UTR_variant	1/3	4
SLC38A8	ENST00000568178.1	c.189+653C>G		intron_variant		5

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

Gnomad4 AFR exome AF: 1.00

Gnomad4 AMR exome AF: 1.00

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.833

Gnomad4 NFE exome AF: 0.825

Gnomad4 OTH exome AF: 0.929

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

Gnomad4 AFR AF: 0.811

Gnomad4 AMR AF: 0.772

Gnomad4 ASJ AF: 0.754

Gnomad4 EAS AF: 0.896

Gnomad4 SAS AF: 0.695

Gnomad4 FIN AF: 0.838

Gnomad4 NFE AF: 0.790

Gnomad4 OTH AF: 0.805

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.78
DANN	Benign	0.29

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: rs12716746; hg19: chr16-84074921;