4-102262778-T-C

Variant names:

• chr4-102262778-T-C
• rs151392
• NM_001135146.2:c.*266A>G

Variant summary

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

The NM_001135146.2(SLC39A8):​c.*266A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.772 in 1,152,272 control chromosomes in the GnomAD database, including 344,950 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.73 (40484 hom., cov: 31)
  • Exomes 𝑓: 0.78 (304466 hom.)
• Consequence: SLC39A8 NM_001135146.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.411
• Publications: 17 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 4-102262778-T-C is Benign according to our data. Variant chr4-102262778-T-C is described in ClinVar as Benign. ClinVar VariationId is 1274972.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.777 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.*266A>G		3_prime_UTR	Exon 9 of 9	NP_001128618.1	Q9C0K1-1
	SLC39A8	NM_022154.5		c.*266A>G		3_prime_UTR	Exon 8 of 8	NP_071437.3	Q9C0K1-1
	SLC39A8	NM_001135148.2		c.*266A>G		3_prime_UTR	Exon 8 of 8	NP_001128620.1	Q9C0K1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC39A8	ENST00000356736.5	TSL:1 MANE Select	c.*266A>G		3_prime_UTR	Exon 9 of 9	ENSP00000349174.4	Q9C0K1-1
	SLC39A8	ENST00000394833.6	TSL:1	c.*266A>G		3_prime_UTR	Exon 8 of 8	ENSP00000378310.2	Q9C0K1-1
	SLC39A8	ENST00000856304.1		c.*266A>G		3_prime_UTR	Exon 10 of 10	ENSP00000526363.1

Frequencies

GnomAD3 genomes AF: 0.726 AC: 110286 AN: 151840 Hom.: 40473 Cov.: 31

Gnomad AFR AF: 0.667

Gnomad AMI AF: 0.781

Gnomad AMR AF: 0.658

Gnomad ASJ AF: 0.825

Gnomad EAS AF: 0.542

Gnomad SAS AF: 0.767

Gnomad FIN AF: 0.730

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.783

Gnomad OTH AF: 0.727

GnomAD4 exome AF: 0.779 AC: 778880 AN: 1000316 Hom.: 304466 Cov.: 26 AF XY: 0.780 AC XY: 367868 AN XY: 471654

African (AFR) AF: 0.670 AC: 13837 AN: 20664

American (AMR) AF: 0.645 AC: 4607 AN: 7146

Ashkenazi Jewish (ASJ) AF: 0.842 AC: 9365 AN: 11124

East Asian (EAS) AF: 0.513 AC: 8099 AN: 15782

South Asian (SAS) AF: 0.762 AC: 21470 AN: 28166

European-Finnish (FIN) AF: 0.736 AC: 7229 AN: 9828

Middle Eastern (MID) AF: 0.795 AC: 1942 AN: 2442

European-Non Finnish (NFE) AF: 0.788 AC: 683741 AN: 867322

Other (OTH) AF: 0.756 AC: 28590 AN: 37842

GnomAD4 genome AF: 0.726 AC: 110336 AN: 151956 Hom.: 40484 Cov.: 31 AF XY: 0.722 AC XY: 53598 AN XY: 74272

African (AFR) AF: 0.667 AC: 27608 AN: 41414

American (AMR) AF: 0.657 AC: 10025 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.825 AC: 2864 AN: 3470

East Asian (EAS) AF: 0.541 AC: 2795 AN: 5164

South Asian (SAS) AF: 0.766 AC: 3688 AN: 4812

European-Finnish (FIN) AF: 0.730 AC: 7711 AN: 10568

Middle Eastern (MID) AF: 0.765 AC: 225 AN: 294

European-Non Finnish (NFE) AF: 0.782 AC: 53167 AN: 67948

Other (OTH) AF: 0.729 AC: 1542 AN: 2116

Alfa AF: 0.761 Hom.: 170476

Bravo AF: 0.717

Asia WGS AF: 0.601 AC: 2086 AN: 3474

ClinVar

ClinVar submissions as Germline

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	-0.83
CADD	Benign	2.2
DANN	Benign	0.46
PhyloP100		-0.41
Mutation Taster		=75/25	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: rs151392; hg19: chr4-103183935;