rs377551

Variant names:

• chr6-160360701-G-A
• rs377551
• NM_021977.4:c.429+11853G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021977.4(SLC22A3):​c.429+11853G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 151,968 control chromosomes in the GnomAD database, including 9,979 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 0.35 (9979 hom., cov: 32)
• Consequence: SLC22A3 NM_021977.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.15
• Publications: 8 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.516 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A3	NM_021977.4	c.429+11853G>A		intron_variant	Intron 1 of 10	ENST00000275300.3	NP_068812.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A3	ENST00000275300.3	c.429+11853G>A		intron_variant	Intron 1 of 10	1	NM_021977.4	ENSP00000275300.2

Frequencies

GnomAD3 genomes AF: 0.346 AC: 52513 AN: 151850 Hom.: 9947 Cov.: 32

Gnomad AFR AF: 0.521

Gnomad AMI AF: 0.195

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.368

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.253

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.349

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.346 AC: 52598 AN: 151968 Hom.: 9979 Cov.: 32 AF XY: 0.342 AC XY: 25424 AN XY: 74282

African (AFR) AF: 0.522 AC: 21625 AN: 41446

American (AMR) AF: 0.236 AC: 3607 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.368 AC: 1276 AN: 3468

East Asian (EAS) AF: 0.305 AC: 1573 AN: 5158

South Asian (SAS) AF: 0.254 AC: 1222 AN: 4820

European-Finnish (FIN) AF: 0.286 AC: 3020 AN: 10560

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.283 AC: 19240 AN: 67926

Other (OTH) AF: 0.350 AC: 739 AN: 2112

Alfa AF: 0.302 Hom.: 11635

Bravo AF: 0.354

Asia WGS AF: 0.314 AC: 1092 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.098
DANN	Benign	0.59
PhyloP100		-4.2
Mutation Taster		=100/0	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: rs377551; hg19: chr6-160781733;