8-22404462-GT-G

Position:

• chr8-22404462-GT-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000381237.6(SLC39A14):​c.-15-221del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 219,734 control chromosomes in the GnomAD database, including 6,143 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.27 (5157 hom., cov: 20)
  • Exomes 𝑓: 0.27 (986 hom.)
• Consequence: SLC39A14 ENST00000381237.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.139

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 -10 ACMG points.

• BP6: Variant 8-22404462-GT-G is Benign according to our data. Variant chr8-22404462-GT-G is described in ClinVar as [Benign]. Clinvar id is 1232290.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.501 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC39A14	NM_001128431.4	c.-15-221del		intron_variant		ENST00000381237.6	NP_001121903.1
SLC39A14	NM_015359.6	c.-15-221del		intron_variant		ENST00000359741.10	NP_056174.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC39A14	ENST00000359741.10	c.-15-221del		intron_variant		2	NM_015359.6	ENSP00000352779	A2
SLC39A14	ENST00000381237.6	c.-15-221del		intron_variant		1	NM_001128431.4	ENSP00000370635	P4

Frequencies

GnomAD3 genomes AF: 0.269 AC: 35463 AN: 131640 Hom.: 5162 Cov.: 20

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.398

Gnomad AMR AF: 0.329

Gnomad ASJ AF: 0.330

Gnomad EAS AF: 0.518

Gnomad SAS AF: 0.383

Gnomad FIN AF: 0.324

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.285

Gnomad OTH AF: 0.281

GnomAD4 exome AF: 0.271 AC: 23884 AN: 88114 Hom.: 986 AF XY: 0.268 AC XY: 12197 AN XY: 45508

Gnomad4 AFR exome AF: 0.275

Gnomad4 AMR exome AF: 0.287

Gnomad4 ASJ exome AF: 0.287

Gnomad4 EAS exome AF: 0.417

Gnomad4 SAS exome AF: 0.178

Gnomad4 FIN exome AF: 0.290

Gnomad4 NFE exome AF: 0.257

Gnomad4 OTH exome AF: 0.274

GnomAD4 genome AF: 0.269 AC: 35453 AN: 131620 Hom.: 5157 Cov.: 20 AF XY: 0.274 AC XY: 17213 AN XY: 62880

Gnomad4 AFR AF: 0.145

Gnomad4 AMR AF: 0.329

Gnomad4 ASJ AF: 0.330

Gnomad4 EAS AF: 0.519

Gnomad4 SAS AF: 0.383

Gnomad4 FIN AF: 0.324

Gnomad4 NFE AF: 0.285

Gnomad4 OTH AF: 0.280

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 16, 2021

- -

Computational scores

Source: dbNSFP v4.3

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: rs61222646; hg19: chr8-22261975;