1-100896280-C-CA

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP5_Moderate

The NM_133496.5(SLC30A7):​c.21dupA​(p.Asp8fs) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

SLC30A7
NM_133496.5 frameshift

Scores

Not classified

Clinical Significance

Likely pathogenic criteria provided, single submitter P:2

Conservation

PhyloP100: 7.87
Variant links:
Genes affected
SLC30A7 (HGNC:19306): (solute carrier family 30 member 7) Zinc functions as a cofactor for numerous enzymes, nuclear factors, and hormones and as an intra- and intercellular signal ion. Members of the zinc transporter (ZNT)/SLC30 subfamily of the cation diffusion facilitator family, such as SLC30A7, permit cellular efflux of zinc (Seve et al., 2004 [PubMed 15154973]).[supplied by OMIM, Mar 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 1-100896280-C-CA is Pathogenic according to our data. Variant chr1-100896280-C-CA is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1711192.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SLC30A7NM_133496.5 linkuse as main transcriptc.21dupA p.Asp8fs frameshift_variant 1/11 ENST00000357650.9 NP_598003.2 Q8NEW0

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SLC30A7ENST00000357650.9 linkuse as main transcriptc.21dupA p.Asp8fs frameshift_variant 1/111 NM_133496.5 ENSP00000350278.4 Q8NEW0
SLC30A7ENST00000370112.8 linkuse as main transcriptc.21dupA p.Asp8fs frameshift_variant 1/121 ENSP00000359130.4 Q8NEW0

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251484
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135920
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000879
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000116
AC:
17
AN:
1461888
Hom.:
0
Cov.:
31
AF XY:
0.0000124
AC XY:
9
AN XY:
727246
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000144
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Likely pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Ziegler-Huang syndrome Pathogenic:1
Pathogenic, no assertion criteria providedliterature onlyOMIMJan 08, 2024- -
Decreased testicular size Pathogenic:1
Likely pathogenic, criteria provided, single submitterclinical testingDepartment of Genetics, CHU d'AngersOct 11, 2022We identified these variants in 2 siblings presenting with the unusual combination of testicular hypoplasia, short stature and bone marrow failure. Decrease of protein level was confirmed by Western blot. The phenotype is similar to the one associated with TP53 (PMID 30146126) which is known to interact with ZNT7. BOth variants were shown to decrease the mRNA level. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1413055215; hg19: chr1-101361836; API