11-63408121-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.488

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]

ACMG classification

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 GnomAd at 44 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC22A9	NM_080866.3	c.1298C>T	p.Thr433Met	missense_variant	8/10	ENST00000279178.4
SLC22A9	XM_047426335.1	c.605C>T	p.Thr202Met	missense_variant	6/8
SLC22A9	XM_017017159.3	c.1288+1410C>T		intron_variant

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0200 AC: 3049 AN: 152160 Hom.: 44 Cov.: 32

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

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.: 30 AF XY: 0.0243 AC XY: 17647 AN XY: 726628

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.: 44 Cov.: 32 AF XY: 0.0199 AC XY: 1481 AN XY: 74456

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.: 89

Bravo AF: 0.0178

TwinsUK AF: 0.0251 AC: 93

ALSPAC AF: 0.0215 AC: 83

ESP6500AA AF: 0.00568 AC: 25

ESP6500EA AF: 0.0280 AC: 241

ExAC AF: 0.0233 AC: 2831

Asia WGS AF: 0.00346 AC: 12 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	T
BayesDel_noAF	Benign	-0.48
Cadd	Benign	15
Dann	Uncertain	1.0
DEOGEN2	Benign	0.40	T
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.15	T
MetaRNN	Benign	0.0078	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.8	M
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.15
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.023	D
Polyphen		1.0	D
Vest4		0.098
MPC		0.027
ClinPred		0.053	T
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

Other links and lift over

dbSNP: rs61742518; hg19: chr11-63175593;