chr8-22400624-G-A

Variant names:

• chr8-22400624-G-A
• rs870215
• NM_001128431.4:c.-15-4072G>A

Variant summary

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

The NM_001351657.2(SLC39A14):​c.16-4072G>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_001351657.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.03
• Publications: 5 publications found

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]

SLC39A14 Gene-Disease associations (from GenCC):

• hypermanganesemia with dystonia 2

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
• hyperostosis cranialis interna

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001351657.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC39A14	NM_001128431.4	MANE Select	c.-15-4072G>A		intron	N/A	NP_001121903.1
	SLC39A14	NM_015359.6	MANE Plus Clinical	c.-15-4072G>A		intron	N/A	NP_056174.2
	SLC39A14	NM_001351657.2		c.16-4072G>A		intron	N/A	NP_001338586.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC39A14	ENST00000359741.10	TSL:2 MANE Plus Clinical	c.-15-4072G>A		intron	N/A	ENSP00000352779.5
	SLC39A14	ENST00000381237.6	TSL:1 MANE Select	c.-15-4072G>A		intron	N/A	ENSP00000370635.1
	SLC39A14	ENST00000240095.10	TSL:1	c.-15-4072G>A		intron	N/A	ENSP00000240095.6

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

African (AFR) AF: 0.439 AC: 18203 AN: 41482

American (AMR) AF: 0.117 AC: 1783 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0401 AC: 139 AN: 3466

East Asian (EAS) AF: 0.179 AC: 926 AN: 5176

South Asian (SAS) AF: 0.113 AC: 545 AN: 4816

European-Finnish (FIN) AF: 0.0241 AC: 256 AN: 10612

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0377 AC: 2564 AN: 68036

Other (OTH) AF: 0.138 AC: 291 AN: 2116

Alfa AF: 0.0534 Hom.: 355

Bravo AF: 0.183

Asia WGS AF: 0.186 AC: 647 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.0040
DANN	Benign	0.49
PhyloP100		-2.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs870215; hg19: chr8-22258137;