16-84033965-C-T

Variant names:

• chr16-84033965-C-T
• rs9922943
• NM_001080442.3:c.389-496G>A

Variant summary

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

The NM_001080442.3(SLC38A8):​c.389-496G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 152,068 control chromosomes in the GnomAD database, including 6,573 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 0.29 (6573 hom., cov: 33)
• Consequence: SLC38A8 NM_001080442.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.30

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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.546 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC38A8	NM_001080442.3	c.389-496G>A		intron_variant	Intron 3 of 10	ENST00000299709.8	NP_001073911.1
SLC38A8	XM_017022946.1	c.389-496G>A		intron_variant	Intron 4 of 11		XP_016878435.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC38A8	ENST00000299709.8	c.389-496G>A		intron_variant	Intron 3 of 10	5	NM_001080442.3	ENSP00000299709.3
SLC38A8	ENST00000568178.1	c.389-496G>A		intron_variant	Intron 3 of 6	5		ENSP00000457737.1
SLC38A8	ENST00000569816.1	c.50-496G>A		intron_variant	Intron 2 of 2	4		ENSP00000455085.1

Frequencies

GnomAD3 genomes AF: 0.287 AC: 43620 AN: 151950 Hom.: 6563 Cov.: 33

Gnomad AFR AF: 0.340

Gnomad AMI AF: 0.200

Gnomad AMR AF: 0.297

Gnomad ASJ AF: 0.315

Gnomad EAS AF: 0.564

Gnomad SAS AF: 0.285

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.235

Gnomad OTH AF: 0.323

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.287 AC: 43656 AN: 152068 Hom.: 6573 Cov.: 33 AF XY: 0.287 AC XY: 21368 AN XY: 74350

Gnomad4 AFR AF: 0.340

Gnomad4 AMR AF: 0.298

Gnomad4 ASJ AF: 0.315

Gnomad4 EAS AF: 0.564

Gnomad4 SAS AF: 0.283

Gnomad4 FIN AF: 0.257

Gnomad4 NFE AF: 0.235

Gnomad4 OTH AF: 0.326

Alfa AF: 0.254 Hom.: 3461

Bravo AF: 0.296

Asia WGS AF: 0.454 AC: 1575 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	0.016
DANN	Benign	0.30

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: rs9922943; hg19: chr16-84067570;