11-63375673-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_080866.3(SLC22A9):c.859A>G(p.Ile287Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: SLC22A9 NM_080866.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.513

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15248567).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC22A9	NM_080866.3	c.859A>G	p.Ile287Val	missense_variant	5/10	ENST00000279178.4
SLC22A9	XM_017017159.3	c.859A>G	p.Ile287Val	missense_variant	5/8
SLC22A9	XM_047426335.1	c.166A>G	p.Ile56Val	missense_variant	3/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC22A9	ENST00000279178.4	c.859A>G	p.Ile287Val	missense_variant	5/10	1	NM_080866.3	P1
SLC22A9	ENST00000536333.5	c.704A>G	p.His235Arg	missense_variant, NMD_transcript_variant	4/7	1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 14, 2023

The c.859A>G (p.I287V) alteration is located in exon 5 (coding exon 5) of the SLC22A9 gene. This alteration results from a A to G substitution at nucleotide position 859, causing the isoleucine (I) at amino acid position 287 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
Cadd	Benign	12
Dann	Uncertain	0.98
DEOGEN2	Benign	0.10	T
Eigen	Benign	0.032
Eigen_PC	Benign	0.014
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.0097	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.3	L
MutationTaster	Benign	1.0	N;N
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.85	N
REVEL	Benign	0.14
Sift	Benign	0.061	T
Sift4G	Benign	0.18	T
Polyphen		0.86	P
Vest4		0.10
MutPred		0.43		Gain of ubiquitination at K291 (P = 0.1008);
MVP		0.16
MPC		0.017
ClinPred		0.41	T
GERP RS		4.9
Varity_R		0.13
gMVP		0.11

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-63143145;