Variant 8-22404670-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000381237.6(SLC39A14):c.-15-26G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 1,590,420 control chromosomes in the GnomAD database, including 38,048 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 7759 hom., cov: 31)

Exomes 𝑓: 0.20 ( 30289 hom. )

Consequence

SLC39A14
ENST00000381237.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.128

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 8-22404670-G-C is Benign according to our data. Variant chr8-22404670-G-C is described in ClinVar as [Benign]. Clinvar id is 1177990.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC39A14	NM_001128431.4 linkuse as main transcript	c.-15-26G>C		intron_variant		ENST00000381237.6	NP_001121903.1
SLC39A14	NM_015359.6 linkuse as main transcript	c.-15-26G>C		intron_variant		ENST00000359741.10	NP_056174.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC39A14	ENST00000359741.10 linkuse as main transcript	c.-15-26G>C		intron_variant		2	NM_015359.6	ENSP00000352779	A2	Q15043-3
SLC39A14	ENST00000381237.6 linkuse as main transcript	c.-15-26G>C		intron_variant		1	NM_001128431.4	ENSP00000370635	P4	Q15043-1

Frequencies

GnomAD3 genomes

AF:

0.283

AC:

42856

AN:

151686

Hom.:

7746

Cov.:

show subpopulations

Gnomad AFR

AF:

0.525

Gnomad AMI

AF:

0.143

Gnomad AMR

AF:

0.181

Gnomad ASJ

AF:

0.164

Gnomad EAS

AF:

0.181

Gnomad SAS

AF:

0.174

Gnomad FIN

AF:

0.222

Gnomad MID

AF:

0.152

Gnomad NFE

AF:

0.193

Gnomad OTH

AF:

0.243

GnomAD3 exomes

AF:

0.203

AC:

47225

AN:

233048

Hom.:

5777

AF XY:

0.197

AC XY:

24828

AN XY:

126052

show subpopulations

Gnomad AFR exome

AF:

0.534

Gnomad AMR exome

AF:

0.140

Gnomad ASJ exome

AF:

0.167

Gnomad EAS exome

AF:

0.189

Gnomad SAS exome

AF:

0.160

Gnomad FIN exome

AF:

0.219

Gnomad NFE exome

AF:

0.189

Gnomad OTH exome

AF:

0.183

GnomAD4 exome

AF:

0.196

AC:

282415

AN:

1438618

Hom.:

30289

Cov.:

AF XY:

0.194

AC XY:

138410

AN XY:

712950

show subpopulations

Gnomad4 AFR exome

AF:

0.534

Gnomad4 AMR exome

AF:

0.142

Gnomad4 ASJ exome

AF:

0.170

Gnomad4 EAS exome

AF:

0.160

Gnomad4 SAS exome

AF:

0.158

Gnomad4 FIN exome

AF:

0.225

Gnomad4 NFE exome

AF:

0.191

Gnomad4 OTH exome

AF:

0.208

GnomAD4 genome

AF:

0.283

AC:

42906

AN:

151802

Hom.:

7759

Cov.:

AF XY:

0.279

AC XY:

20712

AN XY:

74208

show subpopulations

Gnomad4 AFR

AF:

0.525

Gnomad4 AMR

AF:

0.181

Gnomad4 ASJ

AF:

0.164

Gnomad4 EAS

AF:

0.180

Gnomad4 SAS

AF:

0.173

Gnomad4 FIN

AF:

0.222

Gnomad4 NFE

AF:

0.193

Gnomad4 OTH

AF:

0.245

Alfa

AF:

0.230

Hom.:

919

Bravo

AF:

0.291

Asia WGS

AF:

0.259

AC:

903

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 15, 2021	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jul 31, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 28% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy, Progressive Myoclonus Epilepsy and Abnormal Movements and Neurodegeneration with brain iron accumulation. Number of patients: 26. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

6.9

DANN

Benign

0.52

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