8-22404458-G-GTTT

Position:

• chr8-22404458-G-GTTT

Variant summary

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

The ENST00000381237.6(SLC39A14):​c.-15-237_-15-235dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0697 in 278,884 control chromosomes in the GnomAD database, including 1,806 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.16 (1806 hom., cov: 0)
  • Exomes 𝑓: 0.00041 (0 hom.)
• Consequence: SLC39A14 ENST00000381237.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.43

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 8-22404458-G-GTTT is Benign according to our data. Variant chr8-22404458-G-GTTT is described in ClinVar as [Benign]. Clinvar id is 1235882.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.248 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC39A14	NM_001128431.4	c.-15-237_-15-235dup		intron_variant		ENST00000381237.6	NP_001121903.1
SLC39A14	NM_015359.6	c.-15-237_-15-235dup		intron_variant		ENST00000359741.10	NP_056174.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC39A14	ENST00000359741.10	c.-15-237_-15-235dup		intron_variant		2	NM_015359.6	ENSP00000352779	A2
SLC39A14	ENST00000381237.6	c.-15-237_-15-235dup		intron_variant		1	NM_001128431.4	ENSP00000370635	P4

Frequencies

GnomAD3 genomes AF: 0.160 AC: 19353 AN: 121076 Hom.: 1804 Cov.: 0

Gnomad AFR AF: 0.252

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.0883

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.0864

Gnomad SAS AF: 0.0730

Gnomad FIN AF: 0.0922

Gnomad MID AF: 0.0772

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.133

GnomAD4 exome AF: 0.000412 AC: 65 AN: 157766 Hom.: 0 AF XY: 0.000379 AC XY: 31 AN XY: 81804

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000186

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000401

Gnomad4 SAS exome AF: 0.000112

Gnomad4 FIN exome AF: 0.00102

Gnomad4 NFE exome AF: 0.000430

Gnomad4 OTH exome AF: 0.000315

GnomAD4 genome AF: 0.160 AC: 19364 AN: 121118 Hom.: 1806 Cov.: 0 AF XY: 0.152 AC XY: 8804 AN XY: 57766

Gnomad4 AFR AF: 0.252

Gnomad4 AMR AF: 0.0881

Gnomad4 ASJ AF: 0.115

Gnomad4 EAS AF: 0.0862

Gnomad4 SAS AF: 0.0726

Gnomad4 FIN AF: 0.0922

Gnomad4 NFE AF: 0.150

Gnomad4 OTH AF: 0.133

Alfa AF: 0.0468 Hom.: 50

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 24, 2021

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs375772752; hg19: chr8-22261971;