Variant 8-22404585-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_015359.6(SLC39A14):c.-15-111A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.496 in 994,824 control chromosomes in the GnomAD database, including 126,781 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.57 ( 25779 hom., cov: 30)

Exomes 𝑓: 0.48 ( 101002 hom. )

Consequence

SLC39A14
NM_015359.6 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0730

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP6

Variant 8-22404585-A-G is Benign according to our data. Variant chr8-22404585-A-G is described in ClinVar as [Benign]. Clinvar id is 1246155.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.751 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC39A14	NM_001128431.4 linkuse as main transcript	c.-15-111A>G		intron_variant		ENST00000381237.6
SLC39A14	NM_015359.6 linkuse as main transcript	c.-15-111A>G		intron_variant		ENST00000359741.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC39A14	ENST00000359741.10 linkuse as main transcript	c.-15-111A>G		intron_variant		2	NM_015359.6	A2	Q15043-3
SLC39A14	ENST00000381237.6 linkuse as main transcript	c.-15-111A>G		intron_variant		1	NM_001128431.4	P4	Q15043-1

Frequencies

GnomAD3 genomes

AF:

0.570

AC:

86417

AN:

151632

Hom.:

25749

Cov.:

show subpopulations

Gnomad AFR

AF:

0.758

Gnomad AMI

AF:

0.532

Gnomad AMR

AF:

0.513

Gnomad ASJ

AF:

0.486

Gnomad EAS

AF:

0.694

Gnomad SAS

AF:

0.549

Gnomad FIN

AF:

0.533

Gnomad MID

AF:

0.494

Gnomad NFE

AF:

0.472

Gnomad OTH

AF:

0.533

GnomAD4 exome

AF:

0.483

AC:

407163

AN:

843074

Hom.:

101002

Cov.:

AF XY:

0.484

AC XY:

207670

AN XY:

429502

show subpopulations

Gnomad4 AFR exome

AF:

0.751

Gnomad4 AMR exome

AF:

0.501

Gnomad4 ASJ exome

AF:

0.491

Gnomad4 EAS exome

AF:

0.680

Gnomad4 SAS exome

AF:

0.529

Gnomad4 FIN exome

AF:

0.540

Gnomad4 NFE exome

AF:

0.452

Gnomad4 OTH exome

AF:

0.496

GnomAD4 genome

AF:

0.570

AC:

86498

AN:

151750

Hom.:

25779

Cov.:

AF XY:

0.570

AC XY:

42293

AN XY:

74144

show subpopulations

Gnomad4 AFR

AF:

0.759

Gnomad4 AMR

AF:

0.512

Gnomad4 ASJ

AF:

0.486

Gnomad4 EAS

AF:

0.694

Gnomad4 SAS

AF:

0.548

Gnomad4 FIN

AF:

0.533

Gnomad4 NFE

AF:

0.472

Gnomad4 OTH

AF:

0.534

Alfa

AF:

0.530

Hom.:

2813

Bravo

AF:

0.575

Asia WGS

AF:

0.644

AC:

2238

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

3.6

DANN

Benign

0.51

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over