11-63406643-G-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_080866.3(SLC22A9):c.1220G>T(p.Arg407Leu) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC22A9 NM_080866.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.31

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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.967

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC22A9	NM_080866.3	c.1220G>T	p.Arg407Leu	missense_variant	7/10	ENST00000279178.4
SLC22A9	XM_017017159.3	c.1220G>T	p.Arg407Leu	missense_variant	7/8
SLC22A9	XM_047426335.1	c.527G>T	p.Arg176Leu	missense_variant	5/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC22A9	ENST00000279178.4	c.1220G>T	p.Arg407Leu	missense_variant	7/10	1	NM_080866.3	P1
SLC22A9	ENST00000536333.5	c.*348G>T		3_prime_UTR_variant, NMD_transcript_variant	6/7	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Dec 22, 2023

The c.1220G>T (p.R407L) alteration is located in exon 7 (coding exon 7) of the SLC22A9 gene. This alteration results from a G to T substitution at nucleotide position 1220, causing the arginine (R) at amino acid position 407 to be replaced by a leucine (L). 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	Uncertain	0.51
BayesDel_addAF	Benign	0.0017	T
BayesDel_noAF	Benign	-0.24
Cadd	Benign	18
Dann	Uncertain	1.0
DEOGEN2	Uncertain	0.55	D
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.048	N
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.020	T
MetaRNN	Pathogenic	0.97	D
MetaSVM	Benign	-0.55	T
MutationAssessor	Pathogenic	3.8	H
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.25	T
PROVEAN	Pathogenic	-6.2	D
REVEL	Benign	0.23
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.53
MutPred		0.85		Loss of methylation at K402 (P = 0.0447);
MVP		0.40
MPC		0.090
ClinPred		0.98	D
GERP RS		-1.3
Varity_R		0.71
gMVP		0.73

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: chr11-63174115;