chr16-84009786-A-G

Variant names:

• chr16-84009786-A-G
• rs972862727
• NM_001080442.3:c.1306T>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PM4

The NM_001080442.3(SLC38A8):​c.1306T>C​(p.Ter436Argext*?) variant causes a stop lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,461,274 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: SLC38A8 NM_001080442.3 stop_lost
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.01
• Publications: 0 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: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Stoplost variant in NM_001080442.3 Downstream stopcodon found after 8 codons.

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.1306T>C	p.Ter436Argext*?	stop_lost	Exon 11 of 11	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.1306T>C	p.Ter436Argext*?	stop_lost	Exon 11 of 11	ENSP00000299709.3	A6NNN8
	SLC38A8	ENST00000912183.1		c.1306T>C	p.Ter436Argext*?	stop_lost	Exon 12 of 12	ENSP00000582242.1
	SLC38A8	ENST00000946738.1		c.1306T>C	p.Ter436Argext*?	stop_lost	Exon 11 of 11	ENSP00000616797.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1461274 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 726942

African (AFR) AF: 0.00 AC: 0 AN: 33454

American (AMR) AF: 0.00 AC: 0 AN: 44600

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26098

East Asian (EAS) AF: 0.00 AC: 0 AN: 39670

South Asian (SAS) AF: 0.00 AC: 0 AN: 86208

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53396

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1111714

Other (OTH) AF: 0.00 AC: 0 AN: 60368

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	16
DANN	Benign	0.83
Eigen	Uncertain	0.50
Eigen_PC	Benign	0.19
FATHMM_MKL	Benign	0.22	N
PhyloP100		2.0
Vest4		0.033
GERP RS		4.4

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: rs972862727; hg19: chr16-84043391;