8-22404629-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_015359.6(SLC39A14):c.-15-67G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 1,466,832 control chromosomes in the GnomAD database, including 37,682 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.31 (10176 hom., cov: 31)
  • Exomes 𝑓: 0.19 (27506 hom.)
• Consequence: SLC39A14 NM_015359.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.810

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 8-22404629-G-A is Benign according to our data. Variant chr8-22404629-G-A is described in ClinVar as [Benign]. Clinvar id is 1239892.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.619 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC39A14	NM_001128431.4	c.-15-67G>A		intron_variant		ENST00000381237.6
SLC39A14	NM_015359.6	c.-15-67G>A		intron_variant		ENST00000359741.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC39A14	ENST00000359741.10	c.-15-67G>A		intron_variant		2	NM_015359.6	A2
SLC39A14	ENST00000381237.6	c.-15-67G>A		intron_variant		1	NM_001128431.4	P4

Frequencies

GnomAD3 genomes AF: 0.311 AC: 47226 AN: 151692 Hom.: 10160 Cov.: 31

Gnomad AFR AF: 0.625

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.222

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.193

Gnomad OTH AF: 0.267

GnomAD4 exome AF: 0.192 AC: 251871 AN: 1315020 Hom.: 27506 Cov.: 20 AF XY: 0.190 AC XY: 123563 AN XY: 651794

Gnomad4 AFR exome AF: 0.629

Gnomad4 AMR exome AF: 0.146

Gnomad4 ASJ exome AF: 0.168

Gnomad4 EAS exome AF: 0.159

Gnomad4 SAS exome AF: 0.156

Gnomad4 FIN exome AF: 0.225

Gnomad4 NFE exome AF: 0.182

Gnomad4 OTH exome AF: 0.210

GnomAD4 genome AF: 0.311 AC: 47282 AN: 151812 Hom.: 10176 Cov.: 31 AF XY: 0.307 AC XY: 22749 AN XY: 74212

Gnomad4 AFR AF: 0.625

Gnomad4 AMR AF: 0.192

Gnomad4 ASJ AF: 0.163

Gnomad4 EAS AF: 0.179

Gnomad4 SAS AF: 0.174

Gnomad4 FIN AF: 0.222

Gnomad4 NFE AF: 0.193

Gnomad4 OTH AF: 0.268

Alfa AF: 0.269 Hom.: 939

Bravo AF: 0.325

Asia WGS AF: 0.264 AC: 922 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 15, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.17
Dann	Benign	0.62

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: rs896376; hg19: chr8-22262142; COSMIC: COSV51484431;