rs1051647

Positions:

• chr8-22421885-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001128431.4(SLC39A14):​c.*2187T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0515 in 985,304 control chromosomes in the GnomAD database, including 1,357 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.052 (231 hom., cov: 32)
  • Exomes 𝑓: 0.051 (1126 hom.)
• Consequence: SLC39A14 NM_001128431.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.322

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0992 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC39A14	NM_001128431.4	c.*2187T>C		3_prime_UTR_variant	9/9	ENST00000381237.6	NP_001121903.1
SLC39A14	NM_015359.6	c.*2187T>C		3_prime_UTR_variant	9/9	ENST00000359741.10	NP_056174.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC39A14	ENST00000359741.10	c.*2187T>C		3_prime_UTR_variant	9/9	2	NM_015359.6	ENSP00000352779.5
SLC39A14	ENST00000381237.6	c.*2187T>C		3_prime_UTR_variant	9/9	1	NM_001128431.4	ENSP00000370635.1
SLC39A14	ENST00000240095.10	c.1332+4050T>C		intron_variant		1		ENSP00000240095.6

Frequencies

GnomAD3 genomes AF: 0.0520 AC: 7912 AN: 152136 Hom.: 231 Cov.: 32

Gnomad AFR AF: 0.0450

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0539

Gnomad ASJ AF: 0.0464

Gnomad EAS AF: 0.101

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.0384

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0511

Gnomad OTH AF: 0.0517

GnomAD4 exome AF: 0.0514 AC: 42791 AN: 833050 Hom.: 1126 Cov.: 31 AF XY: 0.0512 AC XY: 19710 AN XY: 384686

Gnomad4 AFR exome AF: 0.0454

Gnomad4 AMR exome AF: 0.0478

Gnomad4 ASJ exome AF: 0.0472

Gnomad4 EAS exome AF: 0.0926

Gnomad4 SAS exome AF: 0.100

Gnomad4 FIN exome AF: 0.0399

Gnomad4 NFE exome AF: 0.0501

Gnomad4 OTH exome AF: 0.0553

GnomAD4 genome AF: 0.0520 AC: 7911 AN: 152254 Hom.: 231 Cov.: 32 AF XY: 0.0526 AC XY: 3915 AN XY: 74438

Gnomad4 AFR AF: 0.0449

Gnomad4 AMR AF: 0.0540

Gnomad4 ASJ AF: 0.0464

Gnomad4 EAS AF: 0.101

Gnomad4 SAS AF: 0.107

Gnomad4 FIN AF: 0.0384

Gnomad4 NFE AF: 0.0511

Gnomad4 OTH AF: 0.0531

Alfa AF: 0.0529 Hom.: 221

Bravo AF: 0.0504

Asia WGS AF: 0.106 AC: 369 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.8
DANN	Benign	0.57

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

Other links and lift over

dbSNP: rs1051647; hg19: chr8-22279398;