NM_001135146.2:c.841-15498A>G

Variant names:

• chr4-102283577-T-C
• rs233818
• NM_001135146.2:c.841-15498A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001135146.2(SLC39A8):​c.841-15498A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.749 in 147,412 control chromosomes in the GnomAD database, including 40,936 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 0.75 (40936 hom., cov: 31)
• Consequence: SLC39A8 NM_001135146.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.420
• Publications: 6 publications found

Genes affected

SLC39A8 (HGNC:20862): (solute carrier family 39 member 8) This gene encodes a member of the SLC39 family of solute-carrier genes, which show structural characteristics of zinc transporters. The encoded protein is glycosylated and found in the plasma membrane and mitochondria, and functions in the cellular import of zinc at the onset of inflammation. It is also thought to be the primary transporter of the toxic cation cadmium, which is found in cigarette smoke. Multiple transcript variants encoding different isoforms have been found for this gene. Additional alternatively spliced transcript variants of this gene have been described, but their full-length nature is not known. [provided by RefSeq, Oct 2008]

SLC39A8 Gene-Disease associations (from GenCC):

• SLC39A8-CDG

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Labcorp Genetics (formerly Invitae)
• Leigh syndrome

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.861 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001135146.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC39A8	NM_001135146.2	MANE Select	c.841-15498A>G		intron	N/A	NP_001128618.1
	SLC39A8	NM_022154.5		c.841-15498A>G		intron	N/A	NP_071437.3
	SLC39A8	NM_001135147.1		c.841-15498A>G		intron	N/A	NP_001128619.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC39A8	ENST00000356736.5	TSL:1 MANE Select	c.841-15498A>G		intron	N/A	ENSP00000349174.4
	SLC39A8	ENST00000394833.6	TSL:1	c.841-15498A>G		intron	N/A	ENSP00000378310.2
	SLC39A8	ENST00000856304.1		c.982-13783A>G		intron	N/A	ENSP00000526363.1

Frequencies

GnomAD3 genomes AF: 0.749 AC: 110255 AN: 147294 Hom.: 40890 Cov.: 31

Gnomad AFR AF: 0.869

Gnomad AMI AF: 0.746

Gnomad AMR AF: 0.655

Gnomad ASJ AF: 0.801

Gnomad EAS AF: 0.503

Gnomad SAS AF: 0.705

Gnomad FIN AF: 0.635

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.730

Gnomad OTH AF: 0.720

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.749 AC: 110343 AN: 147412 Hom.: 40936 Cov.: 31 AF XY: 0.740 AC XY: 53127 AN XY: 71760

African (AFR) AF: 0.869 AC: 35865 AN: 41274

American (AMR) AF: 0.653 AC: 9677 AN: 14812

Ashkenazi Jewish (ASJ) AF: 0.801 AC: 2756 AN: 3440

East Asian (EAS) AF: 0.502 AC: 2437 AN: 4852

South Asian (SAS) AF: 0.704 AC: 3240 AN: 4600

European-Finnish (FIN) AF: 0.635 AC: 6092 AN: 9588

Middle Eastern (MID) AF: 0.771 AC: 219 AN: 284

European-Non Finnish (NFE) AF: 0.730 AC: 47906 AN: 65610

Other (OTH) AF: 0.721 AC: 1486 AN: 2060

Alfa AF: 0.758 Hom.: 39528

Bravo AF: 0.771

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.8
DANN	Benign	0.68
PhyloP100		-0.42
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs233818; hg19: chr4-103204734;