rs1045155

Variant names:

• chr4-102262907-C-T
• rs1045155
• NM_001135146.2:c.*137G>A

Your query was ambiguous. Multiple possible variants found:

• chr4-102262907-C-T
• chr4-102262907-C-A

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.*137G>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 0.0152 in 1,409,510 control chromosomes in the GnomAD database, including 2,439 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.074 (1375 hom., cov: 33)
  • Exomes 𝑓: 0.0081 (1064 hom.)
• Consequence: SLC39A8 NM_001135146.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.206
• Publications: 2 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=-0.79).
• BP6: Variant 4-102262907-C-T is Benign according to our data. Variant chr4-102262907-C-T is described in ClinVar as Benign. ClinVar VariationId is 1269086.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.25 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.*137G>A		3_prime_UTR	Exon 9 of 9	NP_001128618.1	Q9C0K1-1
	SLC39A8	NM_022154.5		c.*137G>A		3_prime_UTR	Exon 8 of 8	NP_071437.3	Q9C0K1-1
	SLC39A8	NM_001135148.2		c.*137G>A		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.*137G>A		3_prime_UTR	Exon 9 of 9	ENSP00000349174.4	Q9C0K1-1
	SLC39A8	ENST00000394833.6	TSL:1	c.*137G>A		3_prime_UTR	Exon 8 of 8	ENSP00000378310.2	Q9C0K1-1
	SLC39A8	ENST00000856304.1		c.*137G>A		3_prime_UTR	Exon 10 of 10	ENSP00000526363.1

Frequencies

GnomAD3 genomes AF: 0.0741 AC: 11271 AN: 152102 Hom.: 1374 Cov.: 33

Gnomad AFR AF: 0.254

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0289

Gnomad ASJ AF: 0.00750

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.000471

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.00207

Gnomad OTH AF: 0.0507

GnomAD4 exome AF: 0.00808 AC: 10160 AN: 1257290 Hom.: 1064 Cov.: 31 AF XY: 0.00731 AC XY: 4447 AN XY: 608752

African (AFR) AF: 0.264 AC: 7254 AN: 27492

American (AMR) AF: 0.0215 AC: 367 AN: 17056

Ashkenazi Jewish (ASJ) AF: 0.00644 AC: 117 AN: 18170

East Asian (EAS) AF: 0.00 AC: 0 AN: 34222

South Asian (SAS) AF: 0.000950 AC: 53 AN: 55816

European-Finnish (FIN) AF: 0.000472 AC: 15 AN: 31788

Middle Eastern (MID) AF: 0.0207 AC: 73 AN: 3522

European-Non Finnish (NFE) AF: 0.00130 AC: 1321 AN: 1017154

Other (OTH) AF: 0.0184 AC: 960 AN: 52070

GnomAD4 genome AF: 0.0742 AC: 11291 AN: 152220 Hom.: 1375 Cov.: 33 AF XY: 0.0714 AC XY: 5315 AN XY: 74438

African (AFR) AF: 0.254 AC: 10550 AN: 41490

American (AMR) AF: 0.0289 AC: 442 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00750 AC: 26 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00124 AC: 6 AN: 4828

European-Finnish (FIN) AF: 0.000471 AC: 5 AN: 10612

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.00207 AC: 141 AN: 68026

Other (OTH) AF: 0.0501 AC: 106 AN: 2114

Alfa AF: 0.0285 Hom.: 578

Bravo AF: 0.0849

Asia WGS AF: 0.0120 AC: 43 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	-0.79
CADD	Benign	5.5
DANN	Benign	0.61
PhyloP100		-0.21
Mutation Taster		=100/0	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: rs1045155; hg19: chr4-103184064;