chr4-102253571-T-C

Variant names:

• chr4-102253571-T-C
• rs17032290
• NM_001135147.1:c.1327-141A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001135147.1(SLC39A8):​c.1327-141A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.049 in 458,388 control chromosomes in the GnomAD database, including 694 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.059 (308 hom., cov: 31)
  • Exomes 𝑓: 0.044 (386 hom.)
• Consequence: SLC39A8 NM_001135147.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.16
• Publications: 0 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 4-102253571-T-C is Benign according to our data. Variant chr4-102253571-T-C is described in ClinVar as Benign. ClinVar VariationId is 1280996.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0884 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.1327-141A>G		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.*299-141A>G		intron	N/A	ENSP00000394548.3	A0A804HKX2

Frequencies

GnomAD3 genomes AF: 0.0588 AC: 8943 AN: 152126 Hom.: 307 Cov.: 31

Gnomad AFR AF: 0.0907

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.0515

Gnomad ASJ AF: 0.0308

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0306

Gnomad FIN AF: 0.0284

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0536

Gnomad OTH AF: 0.0536

GnomAD4 exome AF: 0.0442 AC: 13530 AN: 306144 Hom.: 386 AF XY: 0.0444 AC XY: 7046 AN XY: 158846

African (AFR) AF: 0.0938 AC: 744 AN: 7936

American (AMR) AF: 0.0347 AC: 299 AN: 8612

Ashkenazi Jewish (ASJ) AF: 0.0278 AC: 291 AN: 10460

East Asian (EAS) AF: 0.0000419 AC: 1 AN: 23842

South Asian (SAS) AF: 0.0325 AC: 427 AN: 13136

European-Finnish (FIN) AF: 0.0313 AC: 1182 AN: 37712

Middle Eastern (MID) AF: 0.0508 AC: 86 AN: 1694

European-Non Finnish (NFE) AF: 0.0519 AC: 9547 AN: 184086

Other (OTH) AF: 0.0511 AC: 953 AN: 18666

GnomAD4 genome AF: 0.0588 AC: 8953 AN: 152244 Hom.: 308 Cov.: 31 AF XY: 0.0563 AC XY: 4192 AN XY: 74458

African (AFR) AF: 0.0909 AC: 3773 AN: 41526

American (AMR) AF: 0.0514 AC: 786 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0308 AC: 107 AN: 3472

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5190

South Asian (SAS) AF: 0.0300 AC: 145 AN: 4826

European-Finnish (FIN) AF: 0.0284 AC: 301 AN: 10602

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0536 AC: 3647 AN: 68020

Other (OTH) AF: 0.0530 AC: 112 AN: 2112

Alfa AF: 0.0584 Hom.: 26

Bravo AF: 0.0618

Asia WGS AF: 0.0200 AC: 68 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.3
DANN	Benign	0.86
PhyloP100		-1.2
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: rs17032290; hg19: chr4-103174728;