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GeneBe

4-41990735-G-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_006345.4(SLC30A9):c.84G>C(p.Ala28=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0262 in 1,611,134 control chromosomes in the GnomAD database, including 653 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.021 ( 47 hom., cov: 33)
Exomes 𝑓: 0.027 ( 606 hom. )

Consequence

SLC30A9
NM_006345.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.703
Variant links:
Genes affected
SLC30A9 (HGNC:1329): (solute carrier family 30 member 9) Predicted to enable nuclear receptor coactivator activity. Involved in cellular zinc ion homeostasis and zinc ion transport. Located in several cellular components, including cytoplasmic vesicle; cytoskeleton; and endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.71).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 4-41990735-G-C is Benign according to our data. Variant chr4-41990735-G-C is described in ClinVar as [Benign]. Clinvar id is 3057157.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.703 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0209 (3180/152372) while in subpopulation NFE AF= 0.0321 (2184/68030). AF 95% confidence interval is 0.031. There are 47 homozygotes in gnomad4. There are 1500 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 47 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SLC30A9NM_006345.4 linkuse as main transcriptc.84G>C p.Ala28= synonymous_variant 1/18 ENST00000264451.12
SLC30A9XM_047449525.1 linkuse as main transcriptc.84G>C p.Ala28= synonymous_variant 1/13

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SLC30A9ENST00000264451.12 linkuse as main transcriptc.84G>C p.Ala28= synonymous_variant 1/181 NM_006345.4 P1
SLC30A9ENST00000510460.1 linkuse as main transcriptn.209G>C non_coding_transcript_exon_variant 1/42
SLC30A9ENST00000513699.5 linkuse as main transcriptc.84G>C p.Ala28= synonymous_variant, NMD_transcript_variant 1/192

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0209
AC:
3183
AN:
152254
Hom.:
47
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00530
Gnomad AMI
AF:
0.0230
Gnomad AMR
AF:
0.0209
Gnomad ASJ
AF:
0.0311
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.00248
Gnomad FIN
AF:
0.0235
Gnomad MID
AF:
0.0348
Gnomad NFE
AF:
0.0321
Gnomad OTH
AF:
0.0267
GnomAD3 exomes
AF:
0.0211
AC:
5082
AN:
240412
Hom.:
87
AF XY:
0.0215
AC XY:
2846
AN XY:
132110
show subpopulations
Gnomad AFR exome
AF:
0.00445
Gnomad AMR exome
AF:
0.0164
Gnomad ASJ exome
AF:
0.0338
Gnomad EAS exome
AF:
0.0000563
Gnomad SAS exome
AF:
0.00385
Gnomad FIN exome
AF:
0.0241
Gnomad NFE exome
AF:
0.0311
Gnomad OTH exome
AF:
0.0291
GnomAD4 exome
AF:
0.0268
AC:
39029
AN:
1458762
Hom.:
606
Cov.:
33
AF XY:
0.0264
AC XY:
19136
AN XY:
725640
show subpopulations
Gnomad4 AFR exome
AF:
0.00500
Gnomad4 AMR exome
AF:
0.0180
Gnomad4 ASJ exome
AF:
0.0325
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00381
Gnomad4 FIN exome
AF:
0.0246
Gnomad4 NFE exome
AF:
0.0303
Gnomad4 OTH exome
AF:
0.0285
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0209
AC:
3180
AN:
152372
Hom.:
47
Cov.:
33
AF XY:
0.0201
AC XY:
1500
AN XY:
74504
show subpopulations
Gnomad4 AFR
AF:
0.00529
Gnomad4 AMR
AF:
0.0209
Gnomad4 ASJ
AF:
0.0311
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00249
Gnomad4 FIN
AF:
0.0235
Gnomad4 NFE
AF:
0.0321
Gnomad4 OTH
AF:
0.0265
Alfa
AF:
0.0285
Hom.:
25
Bravo
AF:
0.0203
Asia WGS
AF:
0.00433
AC:
15
AN:
3478
EpiCase
AF:
0.0354
EpiControl
AF:
0.0323

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

SLC30A9-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesApr 01, 2019This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.71
Cadd
Benign
8.5
Dann
Benign
0.57
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.2

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: rs16853872; hg19: chr4-41992752; API