Variant chr8-22404462-G-T 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.-15-234G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 218,844 control chromosomes in the GnomAD database, including 7,266 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.28 ( 7256 hom., cov: 22)

Exomes 𝑓: 0.0053 ( 10 hom. )

Consequence

SLC39A14
NM_015359.6 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.42

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=-0.99).

BP6

Variant 8-22404462-G-T is Benign according to our data. Variant chr8-22404462-G-T is described in ClinVar as [Benign]. Clinvar id is 1282183.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.583 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.-15-234G>T		intron_variant		ENST00000381237.6
SLC39A14	NM_015359.6 linkuse as main transcript	c.-15-234G>T		intron_variant		ENST00000359741.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC39A14	ENST00000359741.10 linkuse as main transcript	c.-15-234G>T		intron_variant		2	NM_015359.6	A2	Q15043-3
SLC39A14	ENST00000381237.6 linkuse as main transcript	c.-15-234G>T		intron_variant		1	NM_001128431.4	P4	Q15043-1

Frequencies

GnomAD3 genomes

AF:

0.280

AC:

36331

AN:

129674

Hom.:

7258

Cov.:

show subpopulations

Gnomad AFR

AF:

0.591

Gnomad AMI

AF:

0.137

Gnomad AMR

AF:

0.161

Gnomad ASJ

AF:

0.161

Gnomad EAS

AF:

0.164

Gnomad SAS

AF:

0.162

Gnomad FIN

AF:

0.118

Gnomad MID

AF:

0.136

Gnomad NFE

AF:

0.189

Gnomad OTH

AF:

0.238

GnomAD4 exome

AF:

0.00530

AC:

473

AN:

89188

Hom.:

AF XY:

0.00534

AC XY:

246

AN XY:

46084

show subpopulations

Gnomad4 AFR exome

AF:

0.0194

Gnomad4 AMR exome

AF:

0.00528

Gnomad4 ASJ exome

AF:

0.00272

Gnomad4 EAS exome

AF:

0.00163

Gnomad4 SAS exome

AF:

0.0101

Gnomad4 FIN exome

AF:

0.00554

Gnomad4 NFE exome

AF:

0.00542

Gnomad4 OTH exome

AF:

0.00429

GnomAD4 genome

AF:

0.280

AC:

36331

AN:

129656

Hom.:

7256

Cov.:

AF XY:

0.274

AC XY:

16936

AN XY:

61844

show subpopulations

Gnomad4 AFR

AF:

0.590

Gnomad4 AMR

AF:

0.161

Gnomad4 ASJ

AF:

0.161

Gnomad4 EAS

AF:

0.163

Gnomad4 SAS

AF:

0.160

Gnomad4 FIN

AF:

0.118

Gnomad4 NFE

AF:

0.189

Gnomad4 OTH

AF:

0.239

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

-0.99

CADD

Benign

1.3

DANN

Benign

0.15

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