8-22404541-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_015359.6(SLC39A14):c.-15-155A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0108 in 610,866 control chromosomes in the GnomAD database, including 324 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.033 (259 hom., cov: 31)
  • Exomes 𝑓: 0.0038 (65 hom.)
• Consequence: SLC39A14 NM_015359.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.352

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 8-22404541-A-G is Benign according to our data. Variant chr8-22404541-A-G is described in ClinVar as [Benign]. Clinvar id is 1249284.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC39A14	NM_001128431.4	c.-15-155A>G		intron_variant		ENST00000381237.6
SLC39A14	NM_015359.6	c.-15-155A>G		intron_variant		ENST00000359741.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC39A14	ENST00000359741.10	c.-15-155A>G		intron_variant		2	NM_015359.6	A2
SLC39A14	ENST00000381237.6	c.-15-155A>G		intron_variant		1	NM_001128431.4	P4

Frequencies

GnomAD3 genomes AF: 0.0332 AC: 4852 AN: 146168 Hom.: 259 Cov.: 31

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0125

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000871

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000223

Gnomad OTH AF: 0.0244

GnomAD4 exome AF: 0.00378 AC: 1756 AN: 464594 Hom.: 65 Cov.: 6 AF XY: 0.00310 AC XY: 758 AN XY: 244764

Gnomad4 AFR exome AF: 0.132

Gnomad4 AMR exome AF: 0.00642

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000158

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000176

Gnomad4 OTH exome AF: 0.00895

GnomAD4 genome AF: 0.0331 AC: 4848 AN: 146272 Hom.: 259 Cov.: 31 AF XY: 0.0328 AC XY: 2340 AN XY: 71288

Gnomad4 AFR AF: 0.120

Gnomad4 AMR AF: 0.0124

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000870

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000223

Gnomad4 OTH AF: 0.0242

Alfa AF: 0.0429 Hom.: 36

Bravo AF: 0.0370

Asia WGS AF: 0.00693 AC: 24 AN: 3478

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

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	7.9
Dann	Benign	0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs76009801; hg19: chr8-22262054;