chr4-102253152-C-T

Variant names:

• chr4-102253152-C-T
• rs151371
• NM_001135147.1:c.*270G>A

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.*270G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.573 in 326,126 control chromosomes in the GnomAD database, including 52,513 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.60 (22888 hom., cov: 24)
  • Exomes 𝑓: 0.55 (29625 hom.)
• Consequence: SLC39A8 NM_001135147.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.226
• 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: 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=-0.91).
• BP6: Variant 4-102253152-C-T is Benign according to our data. Variant chr4-102253152-C-T is described in ClinVar as Benign. ClinVar VariationId is 1238663.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.654 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.*270G>A		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.*577G>A		non_coding_transcript_exon	Exon 12 of 12	ENSP00000394548.3	A0A804HKX2
	SLC39A8	ENST00000424970.7	TSL:2	n.*577G>A		3_prime_UTR	Exon 12 of 12	ENSP00000394548.3	A0A804HKX2

Frequencies

GnomAD3 genomes AF: 0.599 AC: 82368 AN: 137598 Hom.: 22866 Cov.: 24

Gnomad AFR AF: 0.661

Gnomad AMI AF: 0.672

Gnomad AMR AF: 0.533

Gnomad ASJ AF: 0.684

Gnomad EAS AF: 0.457

Gnomad SAS AF: 0.493

Gnomad FIN AF: 0.535

Gnomad MID AF: 0.667

Gnomad NFE AF: 0.602

Gnomad OTH AF: 0.590

GnomAD4 exome AF: 0.553 AC: 104285 AN: 188424 Hom.: 29625 Cov.: 0 AF XY: 0.556 AC XY: 53275 AN XY: 95890

African (AFR) AF: 0.544 AC: 3159 AN: 5810

American (AMR) AF: 0.504 AC: 2773 AN: 5498

Ashkenazi Jewish (ASJ) AF: 0.664 AC: 4901 AN: 7378

East Asian (EAS) AF: 0.401 AC: 6808 AN: 16974

South Asian (SAS) AF: 0.407 AC: 1431 AN: 3516

European-Finnish (FIN) AF: 0.503 AC: 6912 AN: 13744

Middle Eastern (MID) AF: 0.574 AC: 799 AN: 1392

European-Non Finnish (NFE) AF: 0.579 AC: 70235 AN: 121252

Other (OTH) AF: 0.565 AC: 7267 AN: 12860

GnomAD4 genome AF: 0.599 AC: 82425 AN: 137702 Hom.: 22888 Cov.: 24 AF XY: 0.593 AC XY: 39692 AN XY: 66944

African (AFR) AF: 0.661 AC: 22420 AN: 33914

American (AMR) AF: 0.532 AC: 7615 AN: 14324

Ashkenazi Jewish (ASJ) AF: 0.684 AC: 2289 AN: 3348

East Asian (EAS) AF: 0.456 AC: 2302 AN: 5050

South Asian (SAS) AF: 0.493 AC: 1947 AN: 3948

European-Finnish (FIN) AF: 0.535 AC: 5138 AN: 9610

Middle Eastern (MID) AF: 0.664 AC: 186 AN: 280

European-Non Finnish (NFE) AF: 0.602 AC: 38792 AN: 64412

Other (OTH) AF: 0.591 AC: 1139 AN: 1928

Alfa AF: 0.568 Hom.: 2982

Bravo AF: 0.555

Asia WGS AF: 0.407 AC: 1413 AN: 3464

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	-0.91
CADD	Benign	3.4
DANN	Benign	0.60
PhyloP100		-0.23
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: rs151371; hg19: chr4-103174309;