rs4872479

chr8-22376123-G-T

Variant summary

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

The NM_015359.6(SLC39A14):c.-16+8715G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 152,030 control chromosomes in the GnomAD database, including 1,632 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 0.11 (1632 hom., cov: 32)
• Consequence: SLC39A14 NM_015359.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.821

Genes affected

SLC39A14 (HGNC:20858): (solute carrier family 39 member 14) This gene encodes a member of the the SLC39A family of divalent metal transporters that mediates the cellular uptake of manganese, zinc, iron, and cadmium. The encoded protein contains eight transmembrane domains, a histidine-rich motif, and a metalloprotease motif, and is expressed on the plasma membrane and the endocytic vesicle membrane. It is an important transporter of nontransferrin-bound iron and a critical regulator of manganese homeostasis. Naturally occurring mutations in this gene are associated with neurodegeneration with brain iron accumulation and early-onset parkinsonism-dystonia with hypermanganesemia. [provided by RefSeq, May 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.255 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC39A14	NM_001128431.4	c.-16+8715G>T		intron_variant		ENST00000381237.6
SLC39A14	NM_015359.6	c.-16+8715G>T		intron_variant		ENST00000359741.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC39A14	ENST00000359741.10	c.-16+8715G>T		intron_variant		2	NM_015359.6	A2
SLC39A14	ENST00000381237.6	c.-16+8715G>T		intron_variant		1	NM_001128431.4	P4

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16796 AN: 151912 Hom.: 1627 Cov.: 32

Gnomad AFR AF: 0.259

Gnomad AMI AF: 0.0800

Gnomad AMR AF: 0.0652

Gnomad ASJ AF: 0.0384

Gnomad EAS AF: 0.0903

Gnomad SAS AF: 0.0470

Gnomad FIN AF: 0.0906

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0451

Gnomad OTH AF: 0.0857

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

GnomAD4 genome AF: 0.111 AC: 16828 AN: 152030 Hom.: 1632 Cov.: 32 AF XY: 0.111 AC XY: 8223 AN XY: 74348

Gnomad4 AFR AF: 0.259

Gnomad4 AMR AF: 0.0653

Gnomad4 ASJ AF: 0.0384

Gnomad4 EAS AF: 0.0901

Gnomad4 SAS AF: 0.0471

Gnomad4 FIN AF: 0.0906

Gnomad4 NFE AF: 0.0450

Gnomad4 OTH AF: 0.0891

Alfa AF: 0.0757 Hom.: 178

Bravo AF: 0.118

Asia WGS AF: 0.106 AC: 369 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.30
Dann	Benign	0.37

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: rs4872479; hg19: chr8-22233636;