8-22404462-GTTTTT-GTTTTTTT

Variant names:

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

Variant summary

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

The NM_001128431.4(SLC39A14):​c.-15-222_-15-221dupTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000186 in 220,984 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 0.0000076 (0 hom., cov: 20)
  • Exomes 𝑓: 0.00045 (0 hom.)
• Consequence: SLC39A14 NM_001128431.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.139

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 afr. gnomad4_exome allele frequency = 0.000448 (40/89232) while in subpopulation AFR AF= 0.00128 (1/780). AF 95% confidence interval is 0.000321. There are 0 homozygotes in gnomad4_exome. There are 24 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_-15-221dupTT		intron_variant	Intron 1 of 8	ENST00000381237.6	NP_001121903.1
SLC39A14	NM_015359.6	c.-15-222_-15-221dupTT		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.-15-234_-15-233insTT		intron_variant	Intron 1 of 8	2	NM_015359.6	ENSP00000352779.5
SLC39A14	ENST00000381237.6	c.-15-234_-15-233insTT		intron_variant	Intron 1 of 8	1	NM_001128431.4	ENSP00000370635.1

Frequencies

GnomAD3 genomes AF: 0.00000759 AC: 1 AN: 131752 Hom.: 0 Cov.: 20

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000155

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000448 AC: 40 AN: 89232 Hom.: 0 AF XY: 0.000521 AC XY: 24 AN XY: 46108

Gnomad4 AFR exome AF: 0.00128

Gnomad4 AMR exome AF: 0.000659

Gnomad4 ASJ exome AF: 0.000905

Gnomad4 EAS exome AF: 0.000148

Gnomad4 SAS exome AF: 0.000480

Gnomad4 FIN exome AF: 0.000347

Gnomad4 NFE exome AF: 0.000455

Gnomad4 OTH exome AF: 0.000357

GnomAD4 genome AF: 0.00000759 AC: 1 AN: 131752 Hom.: 0 Cov.: 20 AF XY: 0.0000159 AC XY: 1 AN XY: 62934

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000155

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

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: rs61222646; hg19: chr8-22261975;