Variant 8-22404715-AGCTGCT-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM4BP6_Very_StrongBA1

The NM_015359.6(SLC39A14):c.14_19del(p.Leu5_Leu6del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.21 in 1,610,574 control chromosomes in the GnomAD database, including 43,103 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.31 ( 10076 hom., cov: 0)

Exomes 𝑓: 0.20 ( 33027 hom. )

Consequence

SLC39A14
NM_015359.6 inframe_deletion

Scores

Not classified

Clinical Significance

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

Conservation

PhyloP100: 4.78

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.

PM4

Nonframeshift variant in NON repetitive region in NM_015359.6.

BP6

Variant 8-22404715-AGCTGCT-A is Benign according to our data. Variant chr8-22404715-AGCTGCT-A is described in ClinVar as [Benign]. Clinvar id is 768230.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.617 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.14_19del	p.Leu5_Leu6del	inframe_deletion	2/9	ENST00000381237.6	NP_001121903.1
SLC39A14	NM_015359.6 linkuse as main transcript	c.14_19del	p.Leu5_Leu6del	inframe_deletion	2/9	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.14_19del	p.Leu5_Leu6del	inframe_deletion	2/9	2	NM_015359.6	ENSP00000352779	A2	Q15043-3
SLC39A14	ENST00000381237.6 linkuse as main transcript	c.14_19del	p.Leu5_Leu6del	inframe_deletion	2/9	1	NM_001128431.4	ENSP00000370635	P4	Q15043-1

Frequencies

GnomAD3 genomes

AF:

0.310

AC:

47014

AN:

151456

Hom.:

10060

Cov.:

show subpopulations

Gnomad AFR

AF:

0.624

Gnomad AMI

AF:

0.142

Gnomad AMR

AF:

0.192

Gnomad ASJ

AF:

0.164

Gnomad EAS

AF:

0.180

Gnomad SAS

AF:

0.176

Gnomad FIN

AF:

0.221

Gnomad MID

AF:

0.156

Gnomad NFE

AF:

0.193

Gnomad OTH

AF:

0.264

GnomAD3 exomes

AF:

0.210

AC:

52123

AN:

248410

Hom.:

7094

AF XY:

0.202

AC XY:

27222

AN XY:

134632

show subpopulations

Gnomad AFR exome

AF:

0.634

Gnomad AMR exome

AF:

0.145

Gnomad ASJ exome

AF:

0.168

Gnomad EAS exome

AF:

0.188

Gnomad SAS exome

AF:

0.161

Gnomad FIN exome

AF:

0.220

Gnomad NFE exome

AF:

0.190

Gnomad OTH exome

AF:

0.189

GnomAD4 exome

AF:

0.200

AC:

291153

AN:

1459000

Hom.:

33027

AF XY:

0.197

AC XY:

142921

AN XY:

725838

show subpopulations

Gnomad4 AFR exome

AF:

0.639

Gnomad4 AMR exome

AF:

0.148

Gnomad4 ASJ exome

AF:

0.169

Gnomad4 EAS exome

AF:

0.160

Gnomad4 SAS exome

AF:

0.159

Gnomad4 FIN exome

AF:

0.225

Gnomad4 NFE exome

AF:

0.192

Gnomad4 OTH exome

AF:

0.216

GnomAD4 genome

AF:

0.311

AC:

47070

AN:

151574

Hom.:

10076

Cov.:

AF XY:

0.306

AC XY:

22640

AN XY:

74098

show subpopulations

Gnomad4 AFR

AF:

0.624

Gnomad4 AMR

AF:

0.192

Gnomad4 ASJ

AF:

0.164

Gnomad4 EAS

AF:

0.179

Gnomad4 SAS

AF:

0.174

Gnomad4 FIN

AF:

0.221

Gnomad4 NFE

AF:

0.193

Gnomad4 OTH

AF:

0.265

Alfa

AF:

0.153

Hom.:

411

Bravo

AF:

0.325

Asia WGS

AF:

0.264

AC:

921

AN:

3478

EpiCase

AF:

0.189

EpiControl

AF:

0.186

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	clinical testing	GeneDx	Jun 29, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

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 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

Splicing

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