Genetic Variant SLC22A9:p.Met113Lys (chr11-63370394-T-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_080866.3(SLC22A9):c.338T>A(p.Met113Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,782 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 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. M113L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SLC22A9
NM_080866.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.732

Publications

0 publications found

Variant links:

Genes affected

SLC22A9 (HGNC:16261): (solute carrier family 22 member 9) Enables anion:anion antiporter activity; short-chain fatty acid transmembrane transporter activity; and sodium-independent organic anion transmembrane transporter activity. Involved in hormone transport; short-chain fatty acid import; and sodium-independent organic anion transport. Located in basolateral plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC22A9 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=0.093896806).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A9	NM_080866.3 link	c.338T>A	p.Met113Lys	missense_variant	Exon 1 of 10	ENST00000279178.4	NP_543142.2	Q8IVM8-1
SLC22A9	XM_017017159.3 link	c.338T>A	p.Met113Lys	missense_variant	Exon 1 of 8		XP_016872648.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A9	ENST00000279178.4 link	c.338T>A	p.Met113Lys	missense_variant	Exon 1 of 10	1	NM_080866.3	ENSP00000279178.3		Q8IVM8-1
SLC22A9	ENST00000536333.5 link	n.338T>A		non_coding_transcript_exon_variant	Exon 1 of 7	1		ENSP00000440206.1		Q8IVM8-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460782

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726682

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33452

American (AMR)

AF:

0.00

AC:

AN:

44674

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26050

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86100

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53368

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5746

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111338

Other (OTH)

AF:

0.00

AC:

AN:

60356

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.088

BayesDel_noAF

Benign

-0.36

CADD

Benign

6.2

(source)

DANN

Benign

0.81

DEOGEN2

Benign

0.045

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.081

LIST_S2

Benign

0.44

M_CAP

Benign

0.0053

MetaRNN

Benign

0.094

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.64

PhyloP100

0.73

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.13

REVEL

Benign

0.21

Sift

Benign

0.036

Sift4G

Benign

0.074

Polyphen

0.0010

Vest4

0.21

MutPred

0.70

Gain of ubiquitination at M113 (P = 0.0069);

MVP

0.11

MPC

0.013

ClinPred

0.34

GERP RS

-0.86

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.26

gMVP

0.65

Mutation Taster

=100/0

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

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over