8-22404458-G-GTTTT

Variant summary

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

The NM_015359.6(SLC39A14):c.-15-235_-15-234insTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0401 in 279,522 control chromosomes in the GnomAD database, including 1,144 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.092 (1143 hom., cov: 0)
  • Exomes 𝑓: 0.00017 (1 hom.)
• Consequence: SLC39A14 NM_015359.6 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-GTTTT is Benign according to our data. Variant chr8-22404458-G-GTTTT is described in ClinVar as [Benign]. Clinvar id is 1265704.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC39A14	NM_001128431.4	c.-15-235_-15-234insTTTT		intron_variant		ENST00000381237.6
SLC39A14	NM_015359.6	c.-15-235_-15-234insTTTT		intron_variant		ENST00000359741.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC39A14	ENST00000359741.10	c.-15-235_-15-234insTTTT		intron_variant		2	NM_015359.6	A2
SLC39A14	ENST00000381237.6	c.-15-235_-15-234insTTTT		intron_variant		1	NM_001128431.4	P4

Frequencies

GnomAD3 genomes AF: 0.0918 AC: 11176 AN: 121680 Hom.: 1143 Cov.: 0

Gnomad AFR AF: 0.250

Gnomad AMI AF: 0.0180

Gnomad AMR AF: 0.0604

Gnomad ASJ AF: 0.0472

Gnomad EAS AF: 0.0999

Gnomad SAS AF: 0.0918

Gnomad FIN AF: 0.00945

Gnomad MID AF: 0.0605

Gnomad NFE AF: 0.0336

Gnomad OTH AF: 0.0924

GnomAD4 exome AF: 0.000171 AC: 27 AN: 157804 Hom.: 1 AF XY: 0.000183 AC XY: 15 AN XY: 81814

Gnomad4 AFR exome AF: 0.00170

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000161

Gnomad4 SAS exome AF: 0.000669

Gnomad4 FIN exome AF: 0.000464

Gnomad4 NFE exome AF: 0.000107

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0918 AC: 11174 AN: 121718 Hom.: 1143 Cov.: 0 AF XY: 0.0921 AC XY: 5350 AN XY: 58118

Gnomad4 AFR AF: 0.249

Gnomad4 AMR AF: 0.0602

Gnomad4 ASJ AF: 0.0472

Gnomad4 EAS AF: 0.0996

Gnomad4 SAS AF: 0.0909

Gnomad4 FIN AF: 0.00945

Gnomad4 NFE AF: 0.0337

Gnomad4 OTH AF: 0.0924

Alfa AF: 0.00527 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 25, 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;