chr11-63408121-C-T

Variant names:

• chr11-63408121-C-T
• rs61742518
• NM_080866.3:c.1298C>T

Variant summary

Our verdict is Benign. The variant received -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. 13/21 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
• Publications: 16 publications found

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

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 44 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080866.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A9	NM_080866.3	MANE Select	c.1298C>T	p.Thr433Met	missense	Exon 8 of 10	NP_543142.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A9	ENST00000279178.4	TSL:1 MANE Select	c.1298C>T	p.Thr433Met	missense	Exon 8 of 10	ENSP00000279178.3
	SLC22A9	ENST00000536333.5	TSL:1	n.*416+1410C>T		intron	N/A	ENSP00000440206.1
	SLC22A9	ENST00000863025.1		c.1298C>T	p.Thr433Met	missense	Exon 8 of 10	ENSP00000533084.1

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

GnomAD2 exomes AF: 0.0225 AC: 5639 AN: 250142 AF XY: 0.0230

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 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

African (AFR) AF: 0.00365 AC: 122 AN: 33442

American (AMR) AF: 0.0161 AC: 718 AN: 44600

Ashkenazi Jewish (ASJ) AF: 0.0386 AC: 1007 AN: 26120

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39670

South Asian (SAS) AF: 0.0132 AC: 1135 AN: 86198

European-Finnish (FIN) AF: 0.0337 AC: 1799 AN: 53380

Middle Eastern (MID) AF: 0.0314 AC: 181 AN: 5760

European-Non Finnish (NFE) AF: 0.0262 AC: 29068 AN: 1111158

Other (OTH) AF: 0.0229 AC: 1381 AN: 60330

GnomAD4 genome AF: 0.0200 AC: 3051 AN: 152278 Hom.: 44 Cov.: 32 AF XY: 0.0199 AC XY: 1481 AN XY: 74456

African (AFR) AF: 0.00507 AC: 211 AN: 41580

American (AMR) AF: 0.0206 AC: 315 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0380 AC: 132 AN: 3472

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5186

South Asian (SAS) AF: 0.0104 AC: 50 AN: 4824

European-Finnish (FIN) AF: 0.0326 AC: 346 AN: 10602

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0283 AC: 1928 AN: 68012

Other (OTH) AF: 0.0218 AC: 46 AN: 2112

Alfa AF: 0.0247 Hom.: 106

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 v4.9

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
PhyloP100		-0.49
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
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs61742518; hg19: chr11-63175593;