rs61742518

Positions:

• chr11-63408121-C-A
• chr11-63408121-C-G
• chr11-63408121-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_080866.3(SLC22A9):​c.1298C>A​(p.Thr433Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,846 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 12/21 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 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 Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.822

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC22A9	NM_080866.3	c.1298C>A	p.Thr433Lys	missense_variant	8/10	ENST00000279178.4	NP_543142.2
SLC22A9	XM_047426335.1	c.605C>A	p.Thr202Lys	missense_variant	6/8		XP_047282291.1
SLC22A9	XM_017017159.3	c.1288+1410C>A		intron_variant			XP_016872648.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC22A9	ENST00000279178.4	c.1298C>A	p.Thr433Lys	missense_variant	8/10	1	NM_080866.3	ENSP00000279178	P1
SLC22A9	ENST00000536333.5	c.*416+1410C>A		intron_variant, NMD_transcript_variant		1		ENSP00000440206

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000400 AC: 1 AN: 250142 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135132

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460846 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726708

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.050	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	13
DANN	Uncertain	0.97
DEOGEN2	Uncertain	0.42	T
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.075	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.018	T
MetaRNN	Pathogenic	0.82	D
MetaSVM	Benign	-0.82	T
MutationAssessor	Pathogenic	3.5	M
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-4.2	D
REVEL	Benign	0.18
Sift	Uncertain	0.010	D
Sift4G	Benign	0.11	T
Polyphen		1.0	D
Vest4		0.57
MutPred		0.69		Gain of ubiquitination at T433 (P = 0.0494);
MVP		0.39
MPC		0.068
ClinPred		0.90	D
GERP RS		1.5
Varity_R		0.24
gMVP		0.44

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

LitVar

Other links and lift over

dbSNP: rs61742518; hg19: chr11-63175593;