Genetic Variant NM_001135146.2:c.*137G>T (chr4-102262907-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001135146.2(SLC39A8):c.*137G>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 0.000000795 in 1,257,344 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: not found (cov: 33)

Exomes 𝑓: 8.0e-7 ( 0 hom. )

Consequence

SLC39A8
NM_001135146.2 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.206

Publications

0 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: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC39A8	NM_001135146.2	MANE Select	c.*137G>T	3_prime_UTR	Exon 9 of 9	NP_001128618.1	Q9C0K1-1
SLC39A8	NM_022154.5		c.*137G>T	3_prime_UTR	Exon 8 of 8	NP_071437.3	Q9C0K1-1
SLC39A8	NM_001135148.2		c.*137G>T	3_prime_UTR	Exon 8 of 8	NP_001128620.1	Q9C0K1-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC39A8	ENST00000356736.5	TSL:1 MANE Select	c.*137G>T	3_prime_UTR	Exon 9 of 9	ENSP00000349174.4	Q9C0K1-1
SLC39A8	ENST00000394833.6	TSL:1	c.*137G>T	3_prime_UTR	Exon 8 of 8	ENSP00000378310.2	Q9C0K1-1
SLC39A8	ENST00000856304.1		c.*137G>T	3_prime_UTR	Exon 10 of 10	ENSP00000526363.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.95e-7

AC:

AN:

1257344

Hom.:

Cov.:

AF XY:

0.00000164

AC XY:

AN XY:

608778

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27530

American (AMR)

AF:

0.00

AC:

AN:

17060

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18172

East Asian (EAS)

AF:

0.00

AC:

AN:

34222

South Asian (SAS)

AF:

0.00

AC:

AN:

55814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31788

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3522

European-Non Finnish (NFE)

AF:

9.83e-7

AC:

AN:

1017162

Other (OTH)

AF:

0.00

AC:

AN:

52074

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

4.5

(source)

DANN

Benign

0.66

PhyloP100

-0.21

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

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