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GeneBe

2-27256387-G-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_003459.5(SLC30A3):c.1017C>A(p.Ile339=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00107 in 1,614,012 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00068 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0011 ( 26 hom. )

Consequence

SLC30A3
NM_003459.5 splice_region, synonymous

Scores

2
Splicing: ADA: 0.00009498
2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.06
Variant links:
Genes affected
SLC30A3 (HGNC:11014): (solute carrier family 30 member 3) Predicted to enable zinc ion transmembrane transporter activity. Involved in regulation of sequestering of zinc ion. Located in late endosome and synaptic vesicle. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 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=-0.41).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 2-27256387-G-T is Benign according to our data. Variant chr2-27256387-G-T is described in ClinVar as [Benign]. Clinvar id is 723115.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=-2.06 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.00111 (1624/1461742) while in subpopulation SAS AF= 0.0158 (1366/86244). AF 95% confidence interval is 0.0151. There are 26 homozygotes in gnomad4_exome. There are 1147 alleles in male gnomad4_exome subpopulation. Median coverage is 31. 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 GnomAdExome at 6 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SLC30A3NM_003459.5 linkuse as main transcriptc.1017C>A p.Ile339= splice_region_variant, synonymous_variant 7/8 ENST00000233535.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SLC30A3ENST00000233535.9 linkuse as main transcriptc.1017C>A p.Ile339= splice_region_variant, synonymous_variant 7/81 NM_003459.5 P1
SLC30A3ENST00000445870.5 linkuse as main transcriptc.830C>A p.Ser277Ter stop_gained, splice_region_variant 6/75
SLC30A3ENST00000482990.1 linkuse as main transcriptn.907C>A non_coding_transcript_exon_variant 3/32
SLC30A3ENST00000497341.5 linkuse as main transcriptn.1670C>A splice_region_variant, non_coding_transcript_exon_variant 3/42

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000677
AC:
103
AN:
152152
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000724
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.0170
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000206
Gnomad OTH
AF:
0.000956
GnomAD3 exomes
AF:
0.00204
AC:
513
AN:
251218
Hom.:
6
AF XY:
0.00285
AC XY:
387
AN XY:
135778
show subpopulations
Gnomad AFR exome
AF:
0.000123
Gnomad AMR exome
AF:
0.0000868
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0153
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000273
Gnomad OTH exome
AF:
0.00131
GnomAD4 exome
AF:
0.00111
AC:
1624
AN:
1461742
Hom.:
26
Cov.:
31
AF XY:
0.00158
AC XY:
1147
AN XY:
727168
show subpopulations
Gnomad4 AFR exome
AF:
0.0000896
Gnomad4 AMR exome
AF:
0.000134
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0158
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000140
Gnomad4 OTH exome
AF:
0.00114
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000683
AC:
104
AN:
152270
Hom.:
0
Cov.:
32
AF XY:
0.00101
AC XY:
75
AN XY:
74466
show subpopulations
Gnomad4 AFR
AF:
0.0000722
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.0172
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000206
Gnomad4 OTH
AF:
0.000946
Alfa
AF:
0.000324
Hom.:
1
Bravo
AF:
0.000219
Asia WGS
AF:
0.00549
AC:
19
AN:
3478
EpiCase
AF:
0.000164
EpiControl
AF:
0.000356

ClinVar

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

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 14, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.41
Cadd
Benign
0.71
Dann
Benign
0.93

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.000095
dbscSNV1_RF
Benign
0.25
SpliceAI score (max)
0.020
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: rs140122355; hg19: chr2-27479255; API