NM_001080442.3:c.*9T>C

Variant names:

• chr16-84009775-A-G
• rs7196330
• NM_001080442.3:c.*9T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001080442.3(SLC38A8):​c.*9T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 1,611,486 control chromosomes in the GnomAD database, including 30,830 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.26 (7292 hom., cov: 32)
  • Exomes 𝑓: 0.17 (23538 hom.)
• Consequence: SLC38A8 NM_001080442.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.248
• Publications: 6 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 16-84009775-A-G is Benign according to our data. Variant chr16-84009775-A-G is described in ClinVar as Benign. ClinVar VariationId is 1261175.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.515 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.*9T>C		3_prime_UTR	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.*9T>C		3_prime_UTR	Exon 11 of 11	ENSP00000299709.3	A6NNN8
	SLC38A8	ENST00000912183.1		c.*9T>C		3_prime_UTR	Exon 12 of 12	ENSP00000582242.1
	SLC38A8	ENST00000946738.1		c.*9T>C		3_prime_UTR	Exon 11 of 11	ENSP00000616797.1

Frequencies

GnomAD3 genomes AF: 0.264 AC: 40107 AN: 151988 Hom.: 7280 Cov.: 32

Gnomad AFR AF: 0.521

Gnomad AMI AF: 0.150

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.178

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.243

GnomAD2 exomes AF: 0.188 AC: 46773 AN: 249004 AF XY: 0.178

Gnomad AFR exome AF: 0.531

Gnomad AMR exome AF: 0.208

Gnomad ASJ exome AF: 0.169

Gnomad EAS exome AF: 0.140

Gnomad FIN exome AF: 0.177

Gnomad NFE exome AF: 0.159

Gnomad OTH exome AF: 0.182

GnomAD4 exome AF: 0.168 AC: 245026 AN: 1459380 Hom.: 23538 Cov.: 31 AF XY: 0.166 AC XY: 120427 AN XY: 725944

African (AFR) AF: 0.533 AC: 17787 AN: 33350

American (AMR) AF: 0.206 AC: 9123 AN: 44190

Ashkenazi Jewish (ASJ) AF: 0.170 AC: 4437 AN: 26062

East Asian (EAS) AF: 0.175 AC: 6944 AN: 39638

South Asian (SAS) AF: 0.137 AC: 11802 AN: 86032

European-Finnish (FIN) AF: 0.175 AC: 9350 AN: 53360

Middle Eastern (MID) AF: 0.190 AC: 1096 AN: 5758

European-Non Finnish (NFE) AF: 0.156 AC: 173615 AN: 1110692

Other (OTH) AF: 0.180 AC: 10872 AN: 60298

GnomAD4 genome AF: 0.264 AC: 40154 AN: 152106 Hom.: 7292 Cov.: 32 AF XY: 0.262 AC XY: 19460 AN XY: 74366

African (AFR) AF: 0.521 AC: 21613 AN: 41464

American (AMR) AF: 0.212 AC: 3242 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.175 AC: 609 AN: 3472

East Asian (EAS) AF: 0.150 AC: 777 AN: 5174

South Asian (SAS) AF: 0.147 AC: 706 AN: 4818

European-Finnish (FIN) AF: 0.178 AC: 1890 AN: 10594

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.156 AC: 10595 AN: 67980

Other (OTH) AF: 0.241 AC: 509 AN: 2114

Alfa AF: 0.213 Hom.: 3262

Bravo AF: 0.283

Asia WGS AF: 0.190 AC: 663 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.89
DANN	Benign	0.28
PhyloP100		-0.25

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7196330; hg19: chr16-84043380; COSMIC: COSV55307056;