rs1051708

Variant names:

• chr8-22422350-A-C
• rs1051708
• NM_001128431.4:c.*2652A>C

Your query was ambiguous. Multiple possible variants found:

• chr8-22422350-A-C
• chr8-22422350-A-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001128431.4(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_001128431.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.103
• Publications: 17 publications found

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 Gene-Disease associations (from GenCC):

• hypermanganesemia with dystonia 2

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
• hyperostosis cranialis interna

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SLC39A14	NM_001128431.4	c.*2652A>C		3_prime_UTR_variant	Exon 9 of 9	ENST00000381237.6	NP_001121903.1
SLC39A14	NM_015359.6	c.*2652A>C		3_prime_UTR_variant	Exon 9 of 9	ENST00000359741.10	NP_056174.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC39A14	ENST00000359741.10	c.*2652A>C		3_prime_UTR_variant	Exon 9 of 9	2	NM_015359.6	ENSP00000352779.5
SLC39A14	ENST00000381237.6	c.*2652A>C		3_prime_UTR_variant	Exon 9 of 9	1	NM_001128431.4	ENSP00000370635.1
SLC39A14	ENST00000240095.10	c.1332+4515A>C		intron_variant	Intron 8 of 8	1		ENSP00000240095.6

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

African (AFR) AF: 0.222 AC: 3499 AN: 15784

American (AMR) AF: 0.411 AC: 404 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.410 AC: 2111 AN: 5152

East Asian (EAS) AF: 0.572 AC: 2074 AN: 3628

South Asian (SAS) AF: 0.503 AC: 8285 AN: 16458

European-Finnish (FIN) AF: 0.426 AC: 289 AN: 678

Middle Eastern (MID) AF: 0.449 AC: 727 AN: 1620

European-Non Finnish (NFE) AF: 0.353 AC: 268669 AN: 761742

Other (OTH) AF: 0.368 AC: 10034 AN: 27294

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

African (AFR) AF: 0.240 AC: 9960 AN: 41500

American (AMR) AF: 0.400 AC: 6103 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.409 AC: 1419 AN: 3472

East Asian (EAS) AF: 0.598 AC: 3088 AN: 5164

South Asian (SAS) AF: 0.507 AC: 2443 AN: 4816

European-Finnish (FIN) AF: 0.386 AC: 4077 AN: 10570

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.362 AC: 24624 AN: 68000

Other (OTH) AF: 0.353 AC: 744 AN: 2106

Alfa AF: 0.354 Hom.: 16429

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
PhyloP100		-0.10
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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