chr11-63375732-T-A

Position:

• chr11-63375732-T-A

Variant summary

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

The NM_080866.3(SLC22A9):​c.918T>A​(p.Ser306Arg) 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. 13/21 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: -0.394

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=0.13492227).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC22A9	NM_080866.3	c.918T>A	p.Ser306Arg	missense_variant	5/10	ENST00000279178.4
SLC22A9	XM_017017159.3	c.918T>A	p.Ser306Arg	missense_variant	5/8
SLC22A9	XM_047426335.1	c.225T>A	p.Ser75Arg	missense_variant	3/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC22A9	ENST00000279178.4	c.918T>A	p.Ser306Arg	missense_variant	5/10	1	NM_080866.3	P1
SLC22A9	ENST00000536333.5	c.*46T>A		3_prime_UTR_variant, NMD_transcript_variant	4/7	1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

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

May 31, 2023

The c.918T>A (p.S306R) alteration is located in exon 5 (coding exon 5) of the SLC22A9 gene. This alteration results from a T to A substitution at nucleotide position 918, causing the serine (S) at amino acid position 306 to be replaced by an arginine (R). 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	Pathogenic	0.57
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.46
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
MutationTaster	Benign	1.0	D;N
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.094
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.058	B
Vest4		0.23
MutPred		0.61		Loss of phosphorylation at S306 (P = 0.0276);
MVP		0.29
MPC		0.013
ClinPred		0.60	D
GERP RS		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.45
gMVP		0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs2014449436; hg19: chr11-63143204;