dbSNP rs1051647: SLC39A14:c.*2187T>C (chr8-22421885-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001128431.4(SLC39A14):c.*2187T>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 0.0515 in 985,304 control chromosomes in the GnomAD database, including 1,357 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 0.052 ( 231 hom., cov: 32)

Exomes 𝑓: 0.051 ( 1126 hom. )

Consequence

SLC39A14
NM_001128431.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.322

Publications

7 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: Labcorp Genetics (formerly Invitae), Orphanet
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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0992 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC39A14	NM_001128431.4 link	c.*2187T>C		3_prime_UTR_variant	Exon 9 of 9	ENST00000381237.6	NP_001121903.1
SLC39A14	NM_015359.6 link	c.*2187T>C		3_prime_UTR_variant	Exon 9 of 9	ENST00000359741.10	NP_056174.2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
SLC39A14	ENST00000359741.10 link	c.*2187T>C	3_prime_UTR_variant	Exon 9 of 9	2	NM_015359.6	ENSP00000352779.5
SLC39A14	ENST00000381237.6 link	c.*2187T>C	3_prime_UTR_variant	Exon 9 of 9	1	NM_001128431.4	ENSP00000370635.1
SLC39A14	ENST00000240095.10 link	c.1332+4050T>C	intron_variant	Intron 8 of 8	1		ENSP00000240095.6

Frequencies

GnomAD3 genomes

AF:

0.0520

AC:

7912

AN:

152136

Hom.:

231

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0450

Gnomad AMI

AF:

0.00987

Gnomad AMR

AF:

0.0539

Gnomad ASJ

AF:

0.0464

Gnomad EAS

AF:

0.101

Gnomad SAS

AF:

0.108

Gnomad FIN

AF:

0.0384

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0511

Gnomad OTH

AF:

0.0517

GnomAD4 exome

AF:

0.0514

AC:

42791

AN:

833050

Hom.:

1126

Cov.:

AF XY:

0.0512

AC XY:

19710

AN XY:

384686

show subpopulations

African (AFR)

AF:

0.0454

AC:

716

AN:

15784

American (AMR)

AF:

0.0478

AC:

AN:

984

Ashkenazi Jewish (ASJ)

AF:

0.0472

AC:

243

AN:

5152

East Asian (EAS)

AF:

0.0926

AC:

336

AN:

3630

South Asian (SAS)

AF:

0.100

AC:

1650

AN:

16456

European-Finnish (FIN)

AF:

0.0399

AC:

AN:

276

Middle Eastern (MID)

AF:

0.0469

AC:

AN:

1620

European-Non Finnish (NFE)

AF:

0.0501

AC:

38202

AN:

761850

Other (OTH)

AF:

0.0553

AC:

1510

AN:

27298

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

2038

4076

6113

8151

10189

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2022

4044

6066

8088

10110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0520

AC:

7911

AN:

152254

Hom.:

231

Cov.:

AF XY:

0.0526

AC XY:

3915

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.0449

AC:

1866

AN:

41554

American (AMR)

AF:

0.0540

AC:

826

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0464

AC:

161

AN:

3470

East Asian (EAS)

AF:

0.101

AC:

521

AN:

5172

South Asian (SAS)

AF:

0.107

AC:

515

AN:

4822

European-Finnish (FIN)

AF:

0.0384

AC:

407

AN:

10612

Middle Eastern (MID)

AF:

0.0612

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0511

AC:

3476

AN:

68018

Other (OTH)

AF:

0.0531

AC:

112

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

380

760

1139

1519

1899

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

204

306

408

510

<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:

0.0528

Hom.:

325

Bravo

AF:

0.0504

Asia WGS

AF:

0.106

AC:

369

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

5.8

(source)

DANN

Benign

0.57

PhyloP100

0.32

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over