NM_001135147.1:c.1327-232C>T

Variant names:

• chr4-102253662-G-A
• rs192068
• NM_001135147.1:c.1327-232C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001135147.1(SLC39A8):​c.1327-232C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.55 in 151,332 control chromosomes in the GnomAD database, including 23,105 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.55 (23105 hom., cov: 30)
• Consequence: SLC39A8 NM_001135147.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.315
• Publications: 5 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 4-102253662-G-A is Benign according to our data. Variant chr4-102253662-G-A is described in ClinVar as Benign. ClinVar VariationId is 1238127.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.569 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001135147.1. 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_001135147.1		c.1327-232C>T		intron	N/A	NP_001128619.1	Q9C0K1-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC39A8	ENST00000424970.7	TSL:2	n.*299-232C>T		intron	N/A	ENSP00000394548.3	A0A804HKX2

Frequencies

GnomAD3 genomes AF: 0.550 AC: 83213 AN: 151214 Hom.: 23083 Cov.: 30

Gnomad AFR AF: 0.553

Gnomad AMI AF: 0.663

Gnomad AMR AF: 0.510

Gnomad ASJ AF: 0.663

Gnomad EAS AF: 0.454

Gnomad SAS AF: 0.418

Gnomad FIN AF: 0.506

Gnomad MID AF: 0.635

Gnomad NFE AF: 0.574

Gnomad OTH AF: 0.548

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

GnomAD4 genome AF: 0.550 AC: 83271 AN: 151332 Hom.: 23105 Cov.: 30 AF XY: 0.544 AC XY: 40206 AN XY: 73852

African (AFR) AF: 0.553 AC: 22806 AN: 41222

American (AMR) AF: 0.508 AC: 7728 AN: 15202

Ashkenazi Jewish (ASJ) AF: 0.663 AC: 2298 AN: 3466

East Asian (EAS) AF: 0.453 AC: 2326 AN: 5134

South Asian (SAS) AF: 0.418 AC: 1988 AN: 4752

European-Finnish (FIN) AF: 0.506 AC: 5267 AN: 10408

Middle Eastern (MID) AF: 0.634 AC: 184 AN: 290

European-Non Finnish (NFE) AF: 0.574 AC: 38920 AN: 67854

Other (OTH) AF: 0.550 AC: 1153 AN: 2098

Alfa AF: 0.560 Hom.: 18582

Bravo AF: 0.555

Asia WGS AF: 0.404 AC: 1408 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.5
DANN	Benign	0.60
PhyloP100		-0.32
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs192068; hg19: chr4-103174819;