Variant 8-22404626-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000381237.6(SLC39A14):c.-15-70C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0395 in 1,442,082 control chromosomes in the GnomAD database, including 1,258 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.032 ( 106 hom., cov: 32)

Exomes 𝑓: 0.040 ( 1152 hom. )

Consequence

SLC39A14
ENST00000381237.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.190

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

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

BP6

Variant 8-22404626-C-T is Benign according to our data. Variant chr8-22404626-C-T is described in ClinVar as [Benign]. Clinvar id is 1222011.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0318 (4832/152120) while in subpopulation NFE AF= 0.0448 (3048/67986). AF 95% confidence interval is 0.0435. There are 106 homozygotes in gnomad4. There are 2455 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 106 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC39A14	NM_001128431.4 linkuse as main transcript	c.-15-70C>T		intron_variant		ENST00000381237.6	NP_001121903.1
SLC39A14	NM_015359.6 linkuse as main transcript	c.-15-70C>T		intron_variant		ENST00000359741.10	NP_056174.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC39A14	ENST00000359741.10 linkuse as main transcript	c.-15-70C>T		intron_variant		2	NM_015359.6	ENSP00000352779	A2	Q15043-3
SLC39A14	ENST00000381237.6 linkuse as main transcript	c.-15-70C>T		intron_variant		1	NM_001128431.4	ENSP00000370635	P4	Q15043-1

Frequencies

GnomAD3 genomes

AF:

0.0318

AC:

4832

AN:

152002

Hom.:

106

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00875

Gnomad AMI

AF:

0.0559

Gnomad AMR

AF:

0.0241

Gnomad ASJ

AF:

0.0230

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.0168

Gnomad FIN

AF:

0.0738

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0448

Gnomad OTH

AF:

0.0278

GnomAD4 exome

AF:

0.0404

AC:

52067

AN:

1289962

Hom.:

1152

Cov.:

AF XY:

0.0399

AC XY:

25521

AN XY:

640234

show subpopulations

Gnomad4 AFR exome

AF:

0.00733

Gnomad4 AMR exome

AF:

0.0124

Gnomad4 ASJ exome

AF:

0.0226

Gnomad4 EAS exome

AF:

0.0000518

Gnomad4 SAS exome

AF:

0.0152

Gnomad4 FIN exome

AF:

0.0692

Gnomad4 NFE exome

AF:

0.0453

Gnomad4 OTH exome

AF:

0.0354

GnomAD4 genome

AF:

0.0318

AC:

4832

AN:

152120

Hom.:

106

Cov.:

AF XY:

0.0330

AC XY:

2455

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.00872

Gnomad4 AMR

AF:

0.0240

Gnomad4 ASJ

AF:

0.0230

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.0168

Gnomad4 FIN

AF:

0.0738

Gnomad4 NFE

AF:

0.0448

Gnomad4 OTH

AF:

0.0275

Alfa

AF:

0.0370

Hom.:

Bravo

AF:

0.0266

Asia WGS

AF:

0.00289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 16, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

3.3

DANN

Benign

0.56

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over