NM_001128431.4:c.-15-222_-15-221delTT

Variant names:

• chr8-22404462-GTT-G
• rs61222646
• NM_001128431.4:c.-15-222_-15-221delTT

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS1

The NM_001128431.4(SLC39A14):​c.-15-222_-15-221delTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00368 in 220,312 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000038 (0 hom., cov: 20)
  • Exomes 𝑓: 0.0091 (0 hom.)
• Consequence: SLC39A14 NM_001128431.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00300

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 Likely_benign. Variant got -4 ACMG points.

• BS1: Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.0091 (806/88560) while in subpopulation EAS AF= 0.0202 (134/6642). AF 95% confidence interval is 0.0174. There are 0 homozygotes in gnomad4_exome. There are 426 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC39A14	NM_001128431.4	c.-15-222_-15-221delTT		intron_variant	Intron 1 of 8	ENST00000381237.6	NP_001121903.1
SLC39A14	NM_015359.6	c.-15-222_-15-221delTT		intron_variant	Intron 1 of 8	ENST00000359741.10	NP_056174.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC39A14	ENST00000359741.10	c.-15-233_-15-232delTT		intron_variant	Intron 1 of 8	2	NM_015359.6	ENSP00000352779.5
SLC39A14	ENST00000381237.6	c.-15-233_-15-232delTT		intron_variant	Intron 1 of 8	1	NM_001128431.4	ENSP00000370635.1

Frequencies

GnomAD3 genomes AF: 0.0000380 AC: 5 AN: 131752 Hom.: 0 Cov.: 20

Gnomad AFR AF: 0.0000304

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000299

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000466

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00910 AC: 806 AN: 88560 Hom.: 0 AF XY: 0.00931 AC XY: 426 AN XY: 45754

Gnomad4 AFR exome AF: 0.00902

Gnomad4 AMR exome AF: 0.0103

Gnomad4 ASJ exome AF: 0.00729

Gnomad4 EAS exome AF: 0.0202

Gnomad4 SAS exome AF: 0.00867

Gnomad4 FIN exome AF: 0.0114

Gnomad4 NFE exome AF: 0.00754

Gnomad4 OTH exome AF: 0.0108

GnomAD4 genome AF: 0.0000380 AC: 5 AN: 131752 Hom.: 0 Cov.: 20 AF XY: 0.0000159 AC XY: 1 AN XY: 62932

Gnomad4 AFR AF: 0.0000304

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.000299

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000466

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs61222646; hg19: chr8-22261975;