11-63373770-G-A

Variant names:

• chr11-63373770-G-A
• rs763519983
• NM_080866.3:c.633G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_080866.3(SLC22A9):​c.633G>A​(p.Met211Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000323 in 1,612,260 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000035 (0 hom.)
• Consequence: SLC22A9 NM_080866.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -3.38
• Publications: 0 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.034311533).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A9	NM_080866.3	c.633G>A	p.Met211Ile	missense_variant	Exon 3 of 10	ENST00000279178.4	NP_543142.2
SLC22A9	XM_017017159.3	c.633G>A	p.Met211Ile	missense_variant	Exon 3 of 8		XP_016872648.1
SLC22A9	XM_047426335.1	c.-32-124G>A		intron_variant	Intron 1 of 7		XP_047282291.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A9	ENST00000279178.4	c.633G>A	p.Met211Ile	missense_variant	Exon 3 of 10	1	NM_080866.3	ENSP00000279178.3
SLC22A9	ENST00000536333.5	n.507-124G>A		intron_variant	Intron 2 of 6	1		ENSP00000440206.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152152 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000923 AC: 23 AN: 249220 AF XY: 0.0000594

Gnomad AFR exome AF: 0.0000617

Gnomad AMR exome AF: 0.000497

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000443

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000349 AC: 51 AN: 1460108 Hom.: 0 Cov.: 31 AF XY: 0.0000220 AC XY: 16 AN XY: 726320

African (AFR) AF: 0.00 AC: 0 AN: 33376

American (AMR) AF: 0.000405 AC: 18 AN: 44480

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25974

East Asian (EAS) AF: 0.00 AC: 0 AN: 39680

South Asian (SAS) AF: 0.00 AC: 0 AN: 85940

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53366

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 0.0000288 AC: 32 AN: 1111226

Other (OTH) AF: 0.0000166 AC: 1 AN: 60314

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152152 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74302

African (AFR) AF: 0.00 AC: 0 AN: 41450

American (AMR) AF: 0.00 AC: 0 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68004

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.000115 AC: 14

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 23, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.633G>A (p.M211I) alteration is located in exon 3 (coding exon 3) of the SLC22A9 gene. This alteration results from a G to A substitution at nucleotide position 633, causing the methionine (M) at amino acid position 211 to be replaced by an isoleucine (I). 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	0.39
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	0.0030
DANN	Benign	0.63
DEOGEN2	Benign	0.084	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0038	N
LIST_S2	Benign	0.21	T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.034	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PhyloP100		-3.4
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.76	N
REVEL	Benign	0.041
Sift	Benign	0.48	T
Sift4G	Benign	0.52	T
Polyphen		0.0030	B
Vest4		0.050
MutPred		0.63		Loss of catalytic residue at M211 (P = 0.1562);
MVP		0.030
MPC		0.013
ClinPred		0.045	T
GERP RS		-8.3
Varity_R		0.053
gMVP		0.29
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs763519983; hg19: chr11-63141242;