chr11-63370173-C-A

Variant names:

• chr11-63370173-C-A
• rs754633521
• NM_080866.3:c.117C>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_080866.3(SLC22A9):​c.117C>A​(p.Asn39Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,770 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: SLC22A9 NM_080866.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.533
• 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: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.93

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080866.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A9	NM_080866.3	MANE Select	c.117C>A	p.Asn39Lys	missense	Exon 1 of 10	NP_543142.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A9	ENST00000279178.4	TSL:1 MANE Select	c.117C>A	p.Asn39Lys	missense	Exon 1 of 10	ENSP00000279178.3	Q8IVM8-1
	SLC22A9	ENST00000536333.5	TSL:1	n.117C>A		non_coding_transcript_exon	Exon 1 of 7	ENSP00000440206.1	Q8IVM8-2
	SLC22A9	ENST00000863025.1		c.117C>A	p.Asn39Lys	missense	Exon 1 of 10	ENSP00000533084.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251174 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000881

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000410 AC: 6 AN: 1461770 Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4 AN XY: 727192

African (AFR) AF: 0.00 AC: 0 AN: 33468

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1111912

Other (OTH) AF: 0.0000166 AC: 1 AN: 60392

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.84
BayesDel_addAF	Benign	-0.082	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.29	T
Eigen	Uncertain	0.24
Eigen_PC	Benign	0.0028
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.0020	T
MetaRNN	Pathogenic	0.93	D
MetaSVM	Benign	-0.81	T
MutationAssessor	Pathogenic	3.8	H
PhyloP100		0.53
PrimateAI	Uncertain	0.49	T
PROVEAN	Pathogenic	-5.7	D
REVEL	Benign	0.25
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.72
MutPred		0.82		Gain of ubiquitination at N39 (P = 0.0369)
MVP		0.19
MPC		0.088
ClinPred		0.99	D
GERP RS		0.50
PromoterAI		-0.012	Neutral
Varity_R		0.83
gMVP		0.78
Mutation Taster		=92/8	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: rs754633521; hg19: chr11-63137645;