Genetic Variant NM_021977.4:c.232T>C (chr6-160348651-T-C) – 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.232T>C(p.Ser78Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S78C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SLC22A3
NM_021977.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0500

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=0.08144483).

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.232T>C	p.Ser78Pro	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.232T>C	p.Ser78Pro	missense	Exon 1 of 11	ENSP00000275300.2	O75751
SLC22A3	ENST00000855214.1		c.232T>C	p.Ser78Pro	missense	Exon 1 of 12	ENSP00000525273.1
SLC22A3	ENST00000855213.1		c.232T>C	p.Ser78Pro	missense	Exon 1 of 7	ENSP00000525272.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1351124

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

666302

African (AFR)

AF:

0.00

AC:

AN:

27452

American (AMR)

AF:

0.00

AC:

AN:

32292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23904

East Asian (EAS)

AF:

0.00

AC:

AN:

31726

South Asian (SAS)

AF:

0.00

AC:

AN:

75986

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33552

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3972

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1065950

Other (OTH)

AF:

0.00

AC:

AN:

56290

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.097

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0063

LIST_S2

Benign

0.24

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.081

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.88

PhyloP100

0.050

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-0.39

REVEL

Benign

0.077

Sift

Benign

0.36

Sift4G

Benign

0.30

Polyphen

0.0

Vest4

0.047

MutPred

0.32

Loss of phosphorylation at S78 (P = 0.0118)

MVP

0.39

MPC

0.47

ClinPred

0.051

GERP RS

-2.1

PromoterAI

-0.0068

Neutral

(source)

Varity_R

0.074

gMVP

0.58

Mutation Taster

=99/1

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over