rs555754

Variant names:

• chr6-160348391-G-A
• rs555754
• NM_021977.4:c.-29G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-160348391-G-A
• chr6-160348391-G-C
• chr6-160348391-G-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_021977.4(SLC22A3):​c.-29G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.469 in 1,429,486 control chromosomes in the GnomAD database, including 159,083 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.49 (18343 hom., cov: 34)
  • Exomes 𝑓: 0.47 (140740 hom.)
• Consequence: SLC22A3 NM_021977.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.716
• Publications: 38 publications found

Genes affected

SLC22A3 (HGNC:10967): (solute carrier family 22 member 3) Polyspecific organic cation transporters in the liver, kidney, intestine, and other organs are critical for elimination of many endogenous small organic cations as well as a wide array of drugs and environmental toxins. This gene is one of three similar cation transporter genes located in a cluster on chromosome 6. The encoded protein contains twelve putative transmembrane domains and is a plasma integral membrane protein. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 6-160348391-G-A is Benign according to our data. Variant chr6-160348391-G-A is described in ClinVar as Benign. ClinVar VariationId is 1241019.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021977.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A3	NM_021977.4	MANE Select	c.-29G>A		5_prime_UTR	Exon 1 of 11	NP_068812.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A3	ENST00000275300.3	TSL:1 MANE Select	c.-29G>A		5_prime_UTR	Exon 1 of 11	ENSP00000275300.2

Frequencies

GnomAD3 genomes AF: 0.489 AC: 74007 AN: 151460 Hom.: 18309 Cov.: 34

Gnomad AFR AF: 0.556

Gnomad AMI AF: 0.396

Gnomad AMR AF: 0.422

Gnomad ASJ AF: 0.550

Gnomad EAS AF: 0.303

Gnomad SAS AF: 0.359

Gnomad FIN AF: 0.495

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.483

Gnomad OTH AF: 0.481

GnomAD2 exomes AF: 0.468 AC: 43965 AN: 93916 AF XY: 0.472

Gnomad AFR exome AF: 0.574

Gnomad AMR exome AF: 0.394

Gnomad ASJ exome AF: 0.559

Gnomad EAS exome AF: 0.338

Gnomad FIN exome AF: 0.516

Gnomad NFE exome AF: 0.495

Gnomad OTH exome AF: 0.505

GnomAD4 exome AF: 0.467 AC: 596530 AN: 1277916 Hom.: 140740 Cov.: 40 AF XY: 0.466 AC XY: 291202 AN XY: 625548

African (AFR) AF: 0.562 AC: 14645 AN: 26058

American (AMR) AF: 0.400 AC: 8662 AN: 21648

Ashkenazi Jewish (ASJ) AF: 0.547 AC: 10140 AN: 18552

East Asian (EAS) AF: 0.299 AC: 9101 AN: 30428

South Asian (SAS) AF: 0.370 AC: 22593 AN: 61000

European-Finnish (FIN) AF: 0.500 AC: 16833 AN: 33668

Middle Eastern (MID) AF: 0.468 AC: 1665 AN: 3560

European-Non Finnish (NFE) AF: 0.474 AC: 488632 AN: 1030636

Other (OTH) AF: 0.463 AC: 24259 AN: 52366

GnomAD4 genome AF: 0.489 AC: 74093 AN: 151570 Hom.: 18343 Cov.: 34 AF XY: 0.487 AC XY: 36062 AN XY: 74078

African (AFR) AF: 0.557 AC: 23071 AN: 41438

American (AMR) AF: 0.421 AC: 6423 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.550 AC: 1905 AN: 3466

East Asian (EAS) AF: 0.303 AC: 1549 AN: 5116

South Asian (SAS) AF: 0.361 AC: 1739 AN: 4822

European-Finnish (FIN) AF: 0.495 AC: 5160 AN: 10426

Middle Eastern (MID) AF: 0.483 AC: 141 AN: 292

European-Non Finnish (NFE) AF: 0.483 AC: 32736 AN: 67748

Other (OTH) AF: 0.480 AC: 1009 AN: 2104

Alfa AF: 0.471 Hom.: 26361

Bravo AF: 0.490

Asia WGS AF: 0.356 AC: 1209 AN: 3394

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	14
DANN	Benign	0.95
PhyloP100		0.72
PromoterAI		0.014	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.3
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs555754; hg19: chr6-160769423; COSMIC: COSV51710349;