NM_001135146.2:c.841-11341T>C

Variant names:

• chr4-102279420-A-G
• rs10014145
• NM_001135146.2:c.841-11341T>C

Variant summary

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

The NM_001135146.2(SLC39A8):​c.841-11341T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 151,968 control chromosomes in the GnomAD database, including 7,671 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 0.31 (7671 hom., cov: 31)
• Consequence: SLC39A8 NM_001135146.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.217
• Publications: 11 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: Labcorp Genetics (formerly Invitae), PanelApp Australia, Orphanet, G2P
• 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=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.356 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.841-11341T>C		intron	N/A	NP_001128618.1	Q9C0K1-1
	SLC39A8	NM_022154.5		c.841-11341T>C		intron	N/A	NP_071437.3	Q9C0K1-1
	SLC39A8	NM_001135147.1		c.841-11341T>C		intron	N/A	NP_001128619.1	Q9C0K1-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC39A8	ENST00000356736.5	TSL:1 MANE Select	c.841-11341T>C		intron	N/A	ENSP00000349174.4	Q9C0K1-1
	SLC39A8	ENST00000394833.6	TSL:1	c.841-11341T>C		intron	N/A	ENSP00000378310.2	Q9C0K1-1
	SLC39A8	ENST00000856304.1		c.982-9626T>C		intron	N/A	ENSP00000526363.1

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47306 AN: 151850 Hom.: 7664 Cov.: 31

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.318

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.328

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.370

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.338

Gnomad NFE AF: 0.322

Gnomad OTH AF: 0.289

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

GnomAD4 genome AF: 0.312 AC: 47343 AN: 151968 Hom.: 7671 Cov.: 31 AF XY: 0.309 AC XY: 22947 AN XY: 74278

African (AFR) AF: 0.346 AC: 14322 AN: 41436

American (AMR) AF: 0.222 AC: 3395 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.328 AC: 1137 AN: 3468

East Asian (EAS) AF: 0.113 AC: 586 AN: 5170

South Asian (SAS) AF: 0.370 AC: 1780 AN: 4810

European-Finnish (FIN) AF: 0.304 AC: 3213 AN: 10566

Middle Eastern (MID) AF: 0.342 AC: 100 AN: 292

European-Non Finnish (NFE) AF: 0.322 AC: 21907 AN: 67944

Other (OTH) AF: 0.291 AC: 614 AN: 2110

Alfa AF: 0.317 Hom.: 16932

Bravo AF: 0.306

Asia WGS AF: 0.241 AC: 838 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	3.3
DANN	Benign	0.60
PhyloP100		-0.22
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: rs10014145; hg19: chr4-103200577;