Variant 8-22404629-G-A 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 NM_001128431.4(SLC39A14):c.-15-67G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 1,466,832 control chromosomes in the GnomAD database, including 37,682 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.31 ( 10176 hom., cov: 31)

Exomes 𝑓: 0.19 ( 27506 hom. )

Consequence

SLC39A14
NM_001128431.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.810

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=-0.93).

BP6

Variant 8-22404629-G-A is Benign according to our data. Variant chr8-22404629-G-A is described in ClinVar as [Benign]. Clinvar id is 1239892.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.619 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC39A14	NM_001128431.4 link	c.-15-67G>A		intron_variant	Intron 1 of 8	ENST00000381237.6	NP_001121903.1	Q15043-1
SLC39A14	NM_015359.6 link	c.-15-67G>A		intron_variant	Intron 1 of 8	ENST00000359741.10	NP_056174.2	Q15043-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC39A14	ENST00000359741.10 link	c.-15-67G>A		intron_variant	Intron 1 of 8	2	NM_015359.6	ENSP00000352779.5		Q15043-3
SLC39A14	ENST00000381237.6 link	c.-15-67G>A		intron_variant	Intron 1 of 8	1	NM_001128431.4	ENSP00000370635.1		Q15043-1

Frequencies

GnomAD3 genomes

AF:

0.311

AC:

47226

AN:

151692

Hom.:

10160

Cov.:

show subpopulations

Gnomad AFR

AF:

0.625

Gnomad AMI

AF:

0.143

Gnomad AMR

AF:

0.192

Gnomad ASJ

AF:

0.163

Gnomad EAS

AF:

0.180

Gnomad SAS

AF:

0.176

Gnomad FIN

AF:

0.222

Gnomad MID

AF:

0.155

Gnomad NFE

AF:

0.193

Gnomad OTH

AF:

0.267

GnomAD4 exome

AF:

0.192

AC:

251871

AN:

1315020

Hom.:

27506

Cov.:

AF XY:

0.190

AC XY:

123563

AN XY:

651794

show subpopulations

Gnomad4 AFR exome

AF:

0.629

Gnomad4 AMR exome

AF:

0.146

Gnomad4 ASJ exome

AF:

0.168

Gnomad4 EAS exome

AF:

0.159

Gnomad4 SAS exome

AF:

0.156

Gnomad4 FIN exome

AF:

0.225

Gnomad4 NFE exome

AF:

0.182

Gnomad4 OTH exome

AF:

0.210

GnomAD4 genome

AF:

0.311

AC:

47282

AN:

151812

Hom.:

10176

Cov.:

AF XY:

0.307

AC XY:

22749

AN XY:

74212

show subpopulations

Gnomad4 AFR

AF:

0.625

Gnomad4 AMR

AF:

0.192

Gnomad4 ASJ

AF:

0.163

Gnomad4 EAS

AF:

0.179

Gnomad4 SAS

AF:

0.174

Gnomad4 FIN

AF:

0.222

Gnomad4 NFE

AF:

0.193

Gnomad4 OTH

AF:

0.268

Alfa

AF:

0.269

Hom.:

939

Bravo

AF:

0.325

Asia WGS

AF:

0.264

AC:

922

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

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 15, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

Jul 31, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 25% 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: 23. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.17

DANN

Benign

0.62

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