Variant 11-63408121-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_080866.3(SLC22A9):c.1298C>T(p.Thr433Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0238 in 1,612,936 control chromosomes in the GnomAD database, including 536 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.020 ( 44 hom., cov: 32)

Exomes 𝑓: 0.024 ( 492 hom. )

Consequence

SLC22A9
NM_080866.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.488

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 made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0077979863).

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.02 (3051/152278) while in subpopulation NFE AF= 0.0283 (1928/68012). AF 95% confidence interval is 0.0273. There are 44 homozygotes in gnomad4. There are 1481 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 44 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SLC22A9	NM_080866.3 linkuse as main transcript	c.1298C>T	p.Thr433Met	missense_variant	8/10	ENST00000279178.4	NP_543142.2
SLC22A9	XM_047426335.1 linkuse as main transcript	c.605C>T	p.Thr202Met	missense_variant	6/8		XP_047282291.1
SLC22A9	XM_017017159.3 linkuse as main transcript	c.1288+1410C>T		intron_variant			XP_016872648.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC22A9	ENST00000279178.4 linkuse as main transcript	c.1298C>T	p.Thr433Met	missense_variant	8/10	1	NM_080866.3	ENSP00000279178	P1	Q8IVM8-1
SLC22A9	ENST00000536333.5 linkuse as main transcript	c.*416+1410C>T		intron_variant, NMD_transcript_variant		1		ENSP00000440206		Q8IVM8-2

Frequencies

GnomAD3 genomes

AF:

0.0200

AC:

3049

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00509

Gnomad AMI

AF:

0.00768

Gnomad AMR

AF:

0.0206

Gnomad ASJ

AF:

0.0380

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.00994

Gnomad FIN

AF:

0.0326

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0283

Gnomad OTH

AF:

0.0220

GnomAD3 exomes

AF:

0.0225

AC:

5639

AN:

250142

Hom.:

106

AF XY:

0.0230

AC XY:

3112

AN XY:

135132

show subpopulations

Gnomad AFR exome

AF:

0.00406

Gnomad AMR exome

AF:

0.0161

Gnomad ASJ exome

AF:

0.0393

Gnomad EAS exome

AF:

0.000164

Gnomad SAS exome

AF:

0.0113

Gnomad FIN exome

AF:

0.0332

Gnomad NFE exome

AF:

0.0301

Gnomad OTH exome

AF:

0.0264

GnomAD4 exome

AF:

0.0242

AC:

35414

AN:

1460658

Hom.:

492

Cov.:

AF XY:

0.0243

AC XY:

17647

AN XY:

726628

show subpopulations

Gnomad4 AFR exome

AF:

0.00365

Gnomad4 AMR exome

AF:

0.0161

Gnomad4 ASJ exome

AF:

0.0386

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0132

Gnomad4 FIN exome

AF:

0.0337

Gnomad4 NFE exome

AF:

0.0262

Gnomad4 OTH exome

AF:

0.0229

GnomAD4 genome

AF:

0.0200

AC:

3051

AN:

152278

Hom.:

Cov.:

AF XY:

0.0199

AC XY:

1481

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.00507

Gnomad4 AMR

AF:

0.0206

Gnomad4 ASJ

AF:

0.0380

Gnomad4 EAS

AF:

0.000578

Gnomad4 SAS

AF:

0.0104

Gnomad4 FIN

AF:

0.0326

Gnomad4 NFE

AF:

0.0283

Gnomad4 OTH

AF:

0.0218

Alfa

AF:

0.0255

Hom.:

Bravo

AF:

0.0178

TwinsUK

AF:

0.0251

AC:

ALSPAC

AF:

0.0215

AC:

ESP6500AA

AF:

0.00568

AC:

ESP6500EA

AF:

0.0280

AC:

241

ExAC

AF:

0.0233

AC:

2831

Asia WGS

AF:

0.00346

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.40

Eigen

Benign

-0.12

Eigen_PC

Benign

-0.39

FATHMM_MKL

Benign

0.019

LIST_S2

Benign

0.15

MetaRNN

Benign

0.0078

MetaSVM

Benign

-0.92

MutationAssessor

Uncertain

2.8

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.28

PROVEAN

Uncertain

-3.6

REVEL

Benign

0.15

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.023

Polyphen

1.0

Vest4

0.098

MPC

0.027

ClinPred

0.053

GERP RS

1.5

Varity_R

0.087

gMVP

0.23

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over