rs2168241

Variant names:

• chr14-69398564-C-G
• rs2168241
• NM_001252151.2:c.-298C>G

Variant summary

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

The NM_001252151.2(SLC39A9):​c.-298C>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 426,140 control chromosomes in the GnomAD database, including 7,299 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 0.19 (2816 hom., cov: 32)
  • Exomes 𝑓: 0.17 (4483 hom.)
• Consequence: SLC39A9 NM_001252151.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0180
• Publications: 6 publications found

Genes affected

SLC39A9 (HGNC:20182): (solute carrier family 39 member 9) Predicted to enable metal ion transmembrane transporter activity. Predicted to be involved in transmembrane transport and zinc ion transport. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC39A9	NM_018375.5	c.-806C>G		upstream_gene_variant		ENST00000336643.10	NP_060845.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC39A9	ENST00000336643.10	c.-806C>G		upstream_gene_variant		1	NM_018375.5	ENSP00000336887.5

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28510 AN: 152032 Hom.: 2813 Cov.: 32

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.108

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.229

Gnomad EAS AF: 0.0584

Gnomad SAS AF: 0.261

Gnomad FIN AF: 0.158

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.187

GnomAD4 exome AF: 0.167 AC: 45840 AN: 273992 Hom.: 4483 Cov.: 0 AF XY: 0.174 AC XY: 25252 AN XY: 144732

African (AFR) AF: 0.231 AC: 1654 AN: 7174

American (AMR) AF: 0.161 AC: 1526 AN: 9460

Ashkenazi Jewish (ASJ) AF: 0.224 AC: 1957 AN: 8722

East Asian (EAS) AF: 0.0506 AC: 814 AN: 16088

South Asian (SAS) AF: 0.250 AC: 8226 AN: 32854

European-Finnish (FIN) AF: 0.168 AC: 2622 AN: 15622

Middle Eastern (MID) AF: 0.196 AC: 245 AN: 1248

European-Non Finnish (NFE) AF: 0.157 AC: 26158 AN: 166586

Other (OTH) AF: 0.162 AC: 2638 AN: 16238

GnomAD4 genome AF: 0.187 AC: 28527 AN: 152148 Hom.: 2816 Cov.: 32 AF XY: 0.188 AC XY: 13995 AN XY: 74372

African (AFR) AF: 0.243 AC: 10102 AN: 41488

American (AMR) AF: 0.184 AC: 2810 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.229 AC: 794 AN: 3470

East Asian (EAS) AF: 0.0587 AC: 304 AN: 5180

South Asian (SAS) AF: 0.262 AC: 1262 AN: 4822

European-Finnish (FIN) AF: 0.158 AC: 1670 AN: 10592

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.162 AC: 11034 AN: 67990

Other (OTH) AF: 0.185 AC: 390 AN: 2108

Alfa AF: 0.178 Hom.: 320

Bravo AF: 0.186

Asia WGS AF: 0.165 AC: 571 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	4.3
DANN	Benign	0.39
PhyloP100		-0.018
PromoterAI		-0.015	Neutral
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2168241; hg19: chr14-69865281;