11-63370394-T-C

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_080866.3(SLC22A9):c.338T>C(p.Met113Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000329 in 1,612,954 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. Variant has been reported in ClinVar as Likely benign (★). 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: 𝑓 0.00018 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

SLC22A9
NM_080866.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007879674).

BP6

Variant 11-63370394-T-C is Benign according to our data. Variant chr11-63370394-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3163500.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A9	NM_080866.3 link	c.338T>C	p.Met113Thr	missense_variant	Exon 1 of 10	ENST00000279178.4	NP_543142.2	Q8IVM8-1
SLC22A9	XM_017017159.3 link	c.338T>C	p.Met113Thr	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>C	p.Met113Thr	missense_variant	Exon 1 of 10	1	NM_080866.3	ENSP00000279178.3		Q8IVM8-1
SLC22A9	ENST00000536333.5 link	n.338T>C		non_coding_transcript_exon_variant	Exon 1 of 7	1		ENSP00000440206.1		Q8IVM8-2

Frequencies

GnomAD3 genomes

AF:

0.000177

AC:

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000603

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000360

AC:

AN:

250174

AF XY:

0.0000296

show subpopulations

Gnomad AFR exome

AF:

0.000369

Gnomad AMR exome

AF:

0.0000580

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000178

AC:

AN:

1460782

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

AN XY:

726682

show subpopulations

African (AFR)

AF:

0.000419

AC:

AN:

33452

American (AMR)

AF:

0.0000448

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:

0.00000540

AC:

AN:

1111338

Other (OTH)

AF:

0.0000497

AC:

AN:

60356

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000177

AC:

AN:

152172

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.000603

AC:

AN:

41460

American (AMR)

AF:

0.0000655

AC:

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68014

Other (OTH)

AF:

0.00

AC:

AN:

2092

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

Alfa

AF:

0.000598

Hom.:

Bravo

AF:

0.000181

ESP6500AA

AF:

0.000682

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000412

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 12, 2024

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.049

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.60

CADD

Benign

0.018

(source)

DANN

Benign

0.56

DEOGEN2

Benign

0.044

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0049

LIST_S2

Benign

0.25

M_CAP

Benign

0.0048

MetaRNN

Benign

0.0079

MetaSVM

Benign

-0.87

MutationAssessor

Benign

-3.6

PhyloP100

0.73

PrimateAI

Benign

0.31

PROVEAN

Benign

4.9

REVEL

Benign

0.15

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0010

Vest4

0.063

MVP

0.061

MPC

0.012

ClinPred

0.017

GERP RS

-0.86

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.033

gMVP

0.40

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

11-63370394-T-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over