Genetic Variant NM_001135147.1:c.*258G>T (chr4-102253164-C-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS1

The NM_001135147.1(SLC39A8):c.*258G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000113 in 353,152 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 26)

Exomes 𝑓: 0.0000049 ( 0 hom. )

Consequence

SLC39A8
NM_001135147.1 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.97

Publications

2 publications found

Variant links:

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

SLC39A8 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.0000202 (3/148502) while in subpopulation EAS AF = 0.000591 (3/5074). AF 95% confidence interval is 0.000161. There are 0 homozygotes in GnomAd4. There are 1 alleles in the male GnomAd4 subpopulation. Median coverage is 26. This position passed quality control check.

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.*258G>T		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.*565G>T		non_coding_transcript_exon	Exon 12 of 12	ENSP00000394548.3	A0A804HKX2
	SLC39A8	ENST00000424970.7	TSL:2	n.*565G>T		3_prime_UTR	Exon 12 of 12	ENSP00000394548.3	A0A804HKX2

Frequencies

GnomAD3 genomes

AF:

0.0000202

AC:

AN:

148384

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000590

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000489

AC:

AN:

204650

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

104074

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

6062

American (AMR)

AF:

0.00

AC:

AN:

5910

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

7918

East Asian (EAS)

AF:

0.00

AC:

AN:

18532

South Asian (SAS)

AF:

0.00

AC:

AN:

3618

European-Finnish (FIN)

AF:

0.00

AC:

AN:

15670

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1682

European-Non Finnish (NFE)

AF:

0.00000761

AC:

AN:

131432

Other (OTH)

AF:

0.00

AC:

AN:

13826

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000202

AC:

AN:

148502

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

72376

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

39984

American (AMR)

AF:

0.00

AC:

AN:

14908

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3436

East Asian (EAS)

AF:

0.000591

AC:

AN:

5074

South Asian (SAS)

AF:

0.00

AC:

AN:

4566

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10166

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67132

Other (OTH)

AF:

0.00

AC:

AN:

2046

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

3014

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.34

(source)

DANN

Benign

0.44

PhyloP100

-3.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over