8-22404715-AGCTGCT-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM4 BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 4.78

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]

ACMG classification

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	UniProt
SLC39A14	NM_001128431.4	c.14_19del	p.Leu5_Leu6del	inframe_deletion	2/9	ENST00000381237.6
SLC39A14	NM_015359.6	c.14_19del	p.Leu5_Leu6del	inframe_deletion	2/9	ENST00000359741.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC39A14	ENST00000359741.10	c.14_19del	p.Leu5_Leu6del	inframe_deletion	2/9	2	NM_015359.6	A2
SLC39A14	ENST00000381237.6	c.14_19del	p.Leu5_Leu6del	inframe_deletion	2/9	1	NM_001128431.4	P4

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47014 AN: 151456 Hom.: 10060 Cov.: 0

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

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

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.: 0 AF XY: 0.306 AC XY: 22640 AN XY: 74098

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:2

Revision: criteria provided, multiple submitters, no conflicts

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	Invitae	Jan 31, 2024	- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3052256; hg19: chr8-22262228;