8-22431482-A-G

Variant names:

• chr8-22431482-A-G
• rs7833266
• ENST00000240095.10:c.1333-2409A>G

Variant summary

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

The ENST00000240095.10(SLC39A14):​c.1333-2409A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 152,012 control chromosomes in the GnomAD database, including 7,640 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 0.31 (7640 hom., cov: 31)
• Consequence: SLC39A14 ENST00000240095.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.84
• Publications: 7 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.485 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC39A14	NM_001135154.3	c.1333-2409A>G		intron_variant	Intron 8 of 8		NP_001128626.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC39A14	ENST00000240095.10	c.1333-2409A>G		intron_variant	Intron 8 of 8	1		ENSP00000240095.6

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47329 AN: 151894 Hom.: 7641 Cov.: 31

Gnomad AFR AF: 0.247

Gnomad AMI AF: 0.449

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.361

Gnomad EAS AF: 0.501

Gnomad SAS AF: 0.402

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.312

Gnomad OTH AF: 0.312

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

GnomAD4 genome AF: 0.312 AC: 47355 AN: 152012 Hom.: 7640 Cov.: 31 AF XY: 0.316 AC XY: 23498 AN XY: 74296

African (AFR) AF: 0.247 AC: 10230 AN: 41450

American (AMR) AF: 0.349 AC: 5333 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.361 AC: 1253 AN: 3470

East Asian (EAS) AF: 0.501 AC: 2592 AN: 5174

South Asian (SAS) AF: 0.402 AC: 1938 AN: 4820

European-Finnish (FIN) AF: 0.346 AC: 3646 AN: 10526

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.312 AC: 21192 AN: 67990

Other (OTH) AF: 0.311 AC: 656 AN: 2110

Alfa AF: 0.314 Hom.: 33113

Bravo AF: 0.307

Asia WGS AF: 0.396 AC: 1376 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.9
DANN	Benign	0.59
PhyloP100		1.8
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7833266; hg19: chr8-22288995;