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GeneBe

6-3273382-G-A

Variant summary

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

The NM_015482.2(SLC22A23):c.1734C>T(p.Ser578=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00224 in 1,612,492 control chromosomes in the GnomAD database, including 84 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.012 ( 47 hom., cov: 33)
Exomes 𝑓: 0.0012 ( 37 hom. )

Consequence

SLC22A23
NM_015482.2 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.250
Variant links:
Genes affected
SLC22A23 (HGNC:21106): (solute carrier family 22 member 23) SLC22A23 belongs to a large family of transmembrane proteins that function as uniporters, symporters, and antiporters to transport organic ions across cell membranes (Jacobsson et al., 2007 [PubMed 17714910]).[supplied by OMIM, Mar 2008]
PSMG4 (HGNC:21108): (proteasome assembly chaperone 4) Predicted to be involved in proteasome assembly. Predicted to be part of protein-containing complex. [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=-0.5).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 6-3273382-G-A is Benign according to our data. Variant chr6-3273382-G-A is described in ClinVar as [Benign]. Clinvar id is 792031.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=0.25 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0121 (1836/152304) while in subpopulation AFR AF= 0.0408 (1698/41570). AF 95% confidence interval is 0.0392. There are 47 homozygotes in gnomad4. There are 860 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
SLC22A23NM_015482.2 linkuse as main transcriptc.1734C>T p.Ser578= synonymous_variant 10/10 ENST00000406686.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SLC22A23ENST00000406686.8 linkuse as main transcriptc.1734C>T p.Ser578= synonymous_variant 10/105 NM_015482.2 P2A1A5C7-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0120
AC:
1830
AN:
152186
Hom.:
47
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0408
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00681
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000118
Gnomad OTH
AF:
0.0110
GnomAD3 exomes
AF:
0.00289
AC:
708
AN:
245106
Hom.:
13
AF XY:
0.00215
AC XY:
287
AN XY:
133516
show subpopulations
Gnomad AFR exome
AF:
0.0387
Gnomad AMR exome
AF:
0.00200
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000481
Gnomad NFE exome
AF:
0.000101
Gnomad OTH exome
AF:
0.00182
GnomAD4 exome
AF:
0.00121
AC:
1768
AN:
1460188
Hom.:
37
Cov.:
32
AF XY:
0.000997
AC XY:
724
AN XY:
726418
show subpopulations
Gnomad4 AFR exome
AF:
0.0422
Gnomad4 AMR exome
AF:
0.00264
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000464
Gnomad4 FIN exome
AF:
0.0000385
Gnomad4 NFE exome
AF:
0.0000315
Gnomad4 OTH exome
AF:
0.00310
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0121
AC:
1836
AN:
152304
Hom.:
47
Cov.:
33
AF XY:
0.0115
AC XY:
860
AN XY:
74476
show subpopulations
Gnomad4 AFR
AF:
0.0408
Gnomad4 AMR
AF:
0.00686
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000414
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000118
Gnomad4 OTH
AF:
0.0109
Alfa
AF:
0.00551
Hom.:
9
Bravo
AF:
0.0138
Asia WGS
AF:
0.00462
AC:
16
AN:
3478
EpiCase
AF:
0.000218
EpiControl
AF:
0.0000593

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 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.50
Cadd
Benign
8.3
Dann
Benign
0.86
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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: rs35042900; hg19: chr6-3273616; COSMIC: COSV66679685; COSMIC: COSV66679685; API