rs35091219

chr6-3271553-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015482.2(SLC22A23):c.*1502G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0852 in 152,358 control chromosomes in the GnomAD database, including 1,489 homozygotes. 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: 𝑓 0.085 (1489 hom., cov: 33)
  • Exomes 𝑓: 0.016 (0 hom.)
• Consequence: SLC22A23 NM_015482.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.498

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.257 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC22A23	NM_015482.2	c.*1502G>A		3_prime_UTR_variant	10/10	ENST00000406686.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC22A23	ENST00000406686.8	c.*1502G>A		3_prime_UTR_variant	10/10	5	NM_015482.2	P2
SLC22A23	ENST00000436008.6	c.*1502G>A		3_prime_UTR_variant	11/11	5		A2
PSMG4	ENST00000451246.2	c.175-10683C>T		intron_variant		3
PSMG4	ENST00000454610.2	c.137+12357C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0852 AC: 12955 AN: 152048 Hom.: 1482 Cov.: 33

Gnomad AFR AF: 0.261

Gnomad AMI AF: 0.0507

Gnomad AMR AF: 0.0396

Gnomad ASJ AF: 0.0228

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0898

Gnomad FIN AF: 0.00113

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0118

Gnomad OTH AF: 0.0727

GnomAD4 exome AF: 0.0156 AC: 3 AN: 192 Hom.: 0 Cov.: 0 AF XY: 0.0259 AC XY: 3 AN XY: 116

Gnomad4 AFR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0145

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0853 AC: 12981 AN: 152166 Hom.: 1489 Cov.: 33 AF XY: 0.0822 AC XY: 6119 AN XY: 74418

Gnomad4 AFR AF: 0.261

Gnomad4 AMR AF: 0.0394

Gnomad4 ASJ AF: 0.0228

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0902

Gnomad4 FIN AF: 0.00113

Gnomad4 NFE AF: 0.0118

Gnomad4 OTH AF: 0.0719

Alfa AF: 0.0345 Hom.: 98

Bravo AF: 0.0956

Asia WGS AF: 0.0490 AC: 169 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	5.0
Dann	Benign	0.61
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs35091219; hg19: chr6-3271787;