chr4-102253334-A-G

Variant names:

• chr4-102253334-A-G
• rs151370
• NM_001135147.1:c.*88T>C

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.*88T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.567 in 680,176 control chromosomes in the GnomAD database, including 113,005 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.62 (30504 hom., cov: 29)
  • Exomes 𝑓: 0.55 (82501 hom.)
• Consequence: SLC39A8 NM_001135147.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.183
• Publications: 8 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 4-102253334-A-G is Benign according to our data. Variant chr4-102253334-A-G is described in ClinVar as Benign. ClinVar VariationId is 1242026.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.794 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.*88T>C		3_prime_UTR	Exon 11 of 11	NP_001128619.1	Q9C0K1-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC39A8	ENST00000424970.7	TSL:2	n.*395T>C		non_coding_transcript_exon	Exon 12 of 12	ENSP00000394548.3	A0A804HKX2
	SLC39A8	ENST00000424970.7	TSL:2	n.*395T>C		3_prime_UTR	Exon 12 of 12	ENSP00000394548.3	A0A804HKX2

Frequencies

GnomAD3 genomes AF: 0.621 AC: 94217 AN: 151640 Hom.: 30465 Cov.: 29

Gnomad AFR AF: 0.801

Gnomad AMI AF: 0.659

Gnomad AMR AF: 0.537

Gnomad ASJ AF: 0.669

Gnomad EAS AF: 0.450

Gnomad SAS AF: 0.417

Gnomad FIN AF: 0.502

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.575

Gnomad OTH AF: 0.594

GnomAD4 exome AF: 0.551 AC: 291295 AN: 528418 Hom.: 82501 Cov.: 0 AF XY: 0.546 AC XY: 155841 AN XY: 285188

African (AFR) AF: 0.795 AC: 11235 AN: 14138

American (AMR) AF: 0.525 AC: 15398 AN: 29352

Ashkenazi Jewish (ASJ) AF: 0.667 AC: 12496 AN: 18726

East Asian (EAS) AF: 0.407 AC: 12335 AN: 30340

South Asian (SAS) AF: 0.425 AC: 23217 AN: 54618

European-Finnish (FIN) AF: 0.498 AC: 23933 AN: 48036

Middle Eastern (MID) AF: 0.603 AC: 2392 AN: 3964

European-Non Finnish (NFE) AF: 0.578 AC: 173376 AN: 300128

Other (OTH) AF: 0.581 AC: 16913 AN: 29116

GnomAD4 genome AF: 0.621 AC: 94298 AN: 151758 Hom.: 30504 Cov.: 29 AF XY: 0.612 AC XY: 45375 AN XY: 74108

African (AFR) AF: 0.801 AC: 33156 AN: 41404

American (AMR) AF: 0.536 AC: 8175 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.669 AC: 2319 AN: 3464

East Asian (EAS) AF: 0.448 AC: 2297 AN: 5122

South Asian (SAS) AF: 0.417 AC: 2005 AN: 4810

European-Finnish (FIN) AF: 0.502 AC: 5255 AN: 10478

Middle Eastern (MID) AF: 0.684 AC: 201 AN: 294

European-Non Finnish (NFE) AF: 0.575 AC: 39034 AN: 67910

Other (OTH) AF: 0.595 AC: 1255 AN: 2110

Alfa AF: 0.608 Hom.: 7705

Bravo AF: 0.639

Asia WGS AF: 0.418 AC: 1458 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	1.6
DANN	Benign	0.70
PhyloP100		-0.18
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: rs151370; hg19: chr4-103174491; COSMIC: COSV70573952;