Genetic Variant NM_021977.4:c.247C>A (chr6-160348666-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_021977.4(SLC22A3):c.247C>A(p.Pro83Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000148 in 1,354,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P83S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

SLC22A3
NM_021977.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0960

Publications

0 publications found

Variant links:

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]

SLC22A3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.077445).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A3	NM_021977.4	MANE Select	c.247C>A	p.Pro83Thr	missense	Exon 1 of 11	NP_068812.1	O75751

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC22A3	ENST00000275300.3	TSL:1 MANE Select	c.247C>A	p.Pro83Thr	missense	Exon 1 of 11	ENSP00000275300.2	O75751
SLC22A3	ENST00000855214.1		c.247C>A	p.Pro83Thr	missense	Exon 1 of 12	ENSP00000525273.1
SLC22A3	ENST00000855213.1		c.247C>A	p.Pro83Thr	missense	Exon 1 of 7	ENSP00000525272.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000148

AC:

AN:

1354894

Hom.:

Cov.:

AF XY:

0.00000150

AC XY:

AN XY:

668148

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27622

American (AMR)

AF:

0.00

AC:

AN:

32896

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23906

East Asian (EAS)

AF:

0.00

AC:

AN:

32354

South Asian (SAS)

AF:

0.00

AC:

AN:

76190

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33546

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3982

European-Non Finnish (NFE)

AF:

0.00000187

AC:

AN:

1067914

Other (OTH)

AF:

0.00

AC:

AN:

56484

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.55

CADD

Benign

3.3

(source)

DANN

Benign

0.72

DEOGEN2

Benign

0.084

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.080

LIST_S2

Benign

0.47

M_CAP

Uncertain

0.15

MetaRNN

Benign

0.077

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.46

PhyloP100

-0.096

PrimateAI

Uncertain

0.77

PROVEAN

Benign

0.22

REVEL

Benign

0.044

Sift

Benign

0.35

Sift4G

Benign

0.57

Polyphen

0.046

Vest4

0.12

MutPred

0.29

Gain of phosphorylation at P83 (P = 0.0013)

MVP

0.42

MPC

0.42

ClinPred

0.18

GERP RS

-1.6

PromoterAI

-0.051

Neutral

(source)

Varity_R

0.031

gMVP

0.58

Mutation Taster

=91/9

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over