rs1051708

chr8-22422350-A-Cchr8-22422350-A-G

Variant summary

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

The NM_015359.6(SLC39A14):c.*2652A>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 0.354 in 985,440 control chromosomes in the GnomAD database, including 62,931 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 0.35 (9862 hom., cov: 32)
  • Exomes 𝑓: 0.36 (53069 hom.)
• Consequence: SLC39A14 NM_015359.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.103

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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.58 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC39A14	NM_001128431.4	c.*2652A>C		3_prime_UTR_variant	9/9	ENST00000381237.6
SLC39A14	NM_015359.6	c.*2652A>C		3_prime_UTR_variant	9/9	ENST00000359741.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC39A14	ENST00000359741.10	c.*2652A>C		3_prime_UTR_variant	9/9	2	NM_015359.6	A2
SLC39A14	ENST00000381237.6	c.*2652A>C		3_prime_UTR_variant	9/9	1	NM_001128431.4	P4
SLC39A14	ENST00000240095.10	c.1332+4515A>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.349 AC: 53045 AN: 151980 Hom.: 9866 Cov.: 32

Gnomad AFR AF: 0.240

Gnomad AMI AF: 0.520

Gnomad AMR AF: 0.400

Gnomad ASJ AF: 0.409

Gnomad EAS AF: 0.599

Gnomad SAS AF: 0.508

Gnomad FIN AF: 0.386

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.362

Gnomad OTH AF: 0.352

GnomAD4 exome AF: 0.355 AC: 296092 AN: 833340 Hom.: 53069 Cov.: 33 AF XY: 0.356 AC XY: 136872 AN XY: 384880

Gnomad4 AFR exome AF: 0.222

Gnomad4 AMR exome AF: 0.411

Gnomad4 ASJ exome AF: 0.410

Gnomad4 EAS exome AF: 0.572

Gnomad4 SAS exome AF: 0.503

Gnomad4 FIN exome AF: 0.426

Gnomad4 NFE exome AF: 0.353

Gnomad4 OTH exome AF: 0.368

GnomAD4 genome AF: 0.349 AC: 53063 AN: 152100 Hom.: 9862 Cov.: 32 AF XY: 0.354 AC XY: 26322 AN XY: 74324

Gnomad4 AFR AF: 0.240

Gnomad4 AMR AF: 0.400

Gnomad4 ASJ AF: 0.409

Gnomad4 EAS AF: 0.598

Gnomad4 SAS AF: 0.507

Gnomad4 FIN AF: 0.386

Gnomad4 NFE AF: 0.362

Gnomad4 OTH AF: 0.353

Alfa AF: 0.358 Hom.: 13160

Bravo AF: 0.342

Asia WGS AF: 0.510 AC: 1772 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	2.1
Dann	Benign	0.41

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: rs1051708; hg19: chr8-22279863; COSMIC: COSV51488012; COSMIC: COSV51488012;