rs870215

Positions:

• chr8-22400624-G-A
• chr8-22400624-G-C
• chr8-22400624-G-T

Variant summary

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

The NM_001128431.4(SLC39A14):​c.-15-4072G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 152,206 control chromosomes in the GnomAD database, including 4,331 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 0.16 (4331 hom., cov: 33)
• Consequence: SLC39A14 NM_001128431.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.03

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.433 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC39A14	NM_001128431.4	c.-15-4072G>A		intron_variant		ENST00000381237.6	NP_001121903.1
SLC39A14	NM_015359.6	c.-15-4072G>A		intron_variant		ENST00000359741.10	NP_056174.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC39A14	ENST00000359741.10	c.-15-4072G>A		intron_variant		2	NM_015359.6	ENSP00000352779.5
SLC39A14	ENST00000381237.6	c.-15-4072G>A		intron_variant		1	NM_001128431.4	ENSP00000370635.1

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24689 AN: 152088 Hom.: 4318 Cov.: 33

Gnomad AFR AF: 0.439

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.0401

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.0241

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0377

Gnomad OTH AF: 0.133

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

GnomAD4 genome AF: 0.163 AC: 24752 AN: 152206 Hom.: 4331 Cov.: 33 AF XY: 0.161 AC XY: 11978 AN XY: 74428

Gnomad4 AFR AF: 0.439

Gnomad4 AMR AF: 0.117

Gnomad4 ASJ AF: 0.0401

Gnomad4 EAS AF: 0.179

Gnomad4 SAS AF: 0.113

Gnomad4 FIN AF: 0.0241

Gnomad4 NFE AF: 0.0377

Gnomad4 OTH AF: 0.138

Alfa AF: 0.0533 Hom.: 324

Bravo AF: 0.183

Asia WGS AF: 0.186 AC: 647 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.0040
DANN	Benign	0.49

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: rs870215; hg19: chr8-22258137;