Variant 11-63382200-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_080866.3(SLC22A9):c.996A>C(p.Gln332His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000177 in 1,583,994 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

SLC22A9
NM_080866.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.131

Variant links:

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]

SLC22A9 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.22735992).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC22A9	NM_080866.3 linkuse as main transcript	c.996A>C	p.Gln332His	missense_variant	6/10	ENST00000279178.4	NP_543142.2	Q8IVM8-1
SLC22A9	XM_017017159.3 linkuse as main transcript	c.996A>C	p.Gln332His	missense_variant	6/8		XP_016872648.1
SLC22A9	XM_047426335.1 linkuse as main transcript	c.303A>C	p.Gln101His	missense_variant	4/8		XP_047282291.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SLC22A9	ENST00000279178.4 linkuse as main transcript	c.996A>C	p.Gln332His	missense_variant	6/10	1	NM_080866.3	ENSP00000279178.3	Q8IVM8-1
SLC22A9	ENST00000536333.5 linkuse as main transcript	n.*124A>C		non_coding_transcript_exon_variant	5/7	1		ENSP00000440206.1	Q8IVM8-2
SLC22A9	ENST00000536333.5 linkuse as main transcript	n.*124A>C		3_prime_UTR_variant	5/7	1		ENSP00000440206.1	Q8IVM8-2

Frequencies

GnomAD3 genomes

AF:

0.0000531

AC:

AN:

150582

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000122

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000210

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000296

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000277

AC:

AN:

180258

Hom.:

AF XY:

0.0000307

AC XY:

AN XY:

97562

show subpopulations

Gnomad AFR exome

AF:

0.000165

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000490

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000239

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000140

AC:

AN:

1433294

Hom.:

Cov.:

AF XY:

0.0000154

AC XY:

AN XY:

713162

show subpopulations

Gnomad4 AFR exome

AF:

0.000123

Gnomad4 AMR exome

AF:

0.0000232

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000359

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000110

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000531

AC:

AN:

150700

Hom.:

Cov.:

AF XY:

0.0000408

AC XY:

AN XY:

73594

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000210

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000296

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000378

ExAC

AF:

0.0000255

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 22, 2024

The c.996A>C (p.Q332H) alteration is located in exon 6 (coding exon 6) of the SLC22A9 gene. This alteration results from a A to C substitution at nucleotide position 996, causing the glutamine (Q) at amino acid position 332 to be replaced by a histidine (H). 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

0.21

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.41

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.0072

LIST_S2

Benign

0.69

M_CAP

Benign

0.0060

MetaRNN

Benign

0.23

MetaSVM

Benign

-0.87

MutationAssessor

Uncertain

2.4

PrimateAI

Uncertain

0.58

PROVEAN

Uncertain

-2.7

REVEL

Benign

0.097

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0080

Polyphen

1.0

Vest4

0.29

MutPred

0.32

Loss of solvent accessibility (P = 0.0561);

MVP

0.37

MPC

0.078

ClinPred

0.96

GERP RS

0.046

Varity_R

0.37

gMVP

0.18

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over