Genetic Variant SLC39A14:c.-15-235_-15-234insTTTTT (chr8-22404458-G-GTTTTT) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001128431.4(SLC39A14):c.-15-235_-15-234insTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000507 in 157,824 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 0.0069 ( 23 hom., cov: 0)

Exomes 𝑓: 0.000051 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SLC39A14
NM_001128431.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.43

Publications

0 publications found

Variant links:

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: PanelApp Australia, Orphanet, Labcorp Genetics (formerly Invitae)
hyperostosis cranialis interna
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

SLC39A14 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001128431.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC39A14	NM_001128431.4	MANE Select	c.-15-235_-15-234insTTTTT	intron	N/A	NP_001121903.1	Q15043-1
SLC39A14	NM_015359.6	MANE Plus Clinical	c.-15-235_-15-234insTTTTT	intron	N/A	NP_056174.2	Q15043-3
SLC39A14	NM_001351657.2		c.16-235_16-234insTTTTT	intron	N/A	NP_001338586.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC39A14	ENST00000359741.10	TSL:2 MANE Plus Clinical	c.-15-238_-15-237insTTTTT	intron	N/A	ENSP00000352779.5	Q15043-3
SLC39A14	ENST00000381237.6	TSL:1 MANE Select	c.-15-238_-15-237insTTTTT	intron	N/A	ENSP00000370635.1	Q15043-1
SLC39A14	ENST00000240095.10	TSL:1	c.-15-238_-15-237insTTTTT	intron	N/A	ENSP00000240095.6	Q15043-2

Frequencies

GnomAD3 genomes

AF:

0.00687

AC:

843

AN:

122628

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0254

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00406

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00165

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000392

Gnomad OTH

AF:

0.00351

GnomAD4 exome

AF:

0.0000507

AC:

AN:

157824

Hom.:

AF XY:

0.0000489

AC XY:

AN XY:

81826

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

1764

American (AMR)

AF:

0.00

AC:

AN:

5366

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

5696

East Asian (EAS)

AF:

0.00

AC:

AN:

12460

South Asian (SAS)

AF:

0.000112

AC:

AN:

8966

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10784

Middle Eastern (MID)

AF:

0.00

AC:

AN:

832

European-Non Finnish (NFE)

AF:

0.0000586

AC:

AN:

102404

Other (OTH)

AF:

0.000105

AC:

AN:

9552

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00690

AC:

846

AN:

122664

Hom.:

Cov.:

AF XY:

0.00662

AC XY:

388

AN XY:

58568

show subpopulations

African (AFR)

AF:

0.0255

AC:

757

AN:

29702

American (AMR)

AF:

0.00406

AC:

AN:

12080

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3104

East Asian (EAS)

AF:

0.00165

AC:

AN:

3640

South Asian (SAS)

AF:

0.00105

AC:

AN:

3818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6368

Middle Eastern (MID)

AF:

0.00

AC:

AN:

232

European-Non Finnish (NFE)

AF:

0.000392

AC:

AN:

61220

Other (OTH)

AF:

0.00349

AC:

AN:

1720

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.441

Heterozygous variant carriers

105

131

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.4

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over