Genetic Variant SLC22A9:p.Lys334Thr (chr11-63382205-A-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_080866.3(SLC22A9):c.1001A>C(p.Lys334Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000174 in 1,609,990 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

SLC22A9
NM_080866.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.50

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11062533).

BP6

Variant 11-63382205-A-C is Benign according to our data. Variant chr11-63382205-A-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3443230.Status of the report is criteria_provided_single_submitter, 1 stars.

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.1001A>C	p.Lys334Thr	missense	Exon 6 of 10	NP_543142.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC22A9	ENST00000279178.4	TSL:1 MANE Select	c.1001A>C	p.Lys334Thr	missense	Exon 6 of 10	ENSP00000279178.3	Q8IVM8-1
SLC22A9	ENST00000536333.5	TSL:1	n.*129A>C		non_coding_transcript_exon	Exon 5 of 7	ENSP00000440206.1	Q8IVM8-2
SLC22A9	ENST00000536333.5	TSL:1	n.*129A>C		3_prime_UTR	Exon 5 of 7	ENSP00000440206.1	Q8IVM8-2

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000171

AC:

AN:

1457858

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

AN XY:

725046

show subpopulations

African (AFR)

AF:

0.0000604

AC:

AN:

33130

American (AMR)

AF:

0.00

AC:

AN:

44004

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26036

East Asian (EAS)

AF:

0.00

AC:

AN:

39668

South Asian (SAS)

AF:

0.00

AC:

AN:

84816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53380

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.0000207

AC:

AN:

1110854

Other (OTH)

AF:

0.00

AC:

AN:

60216

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152132

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74314

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41414

American (AMR)

AF:

0.00

AC:

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68040

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.542

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000847

Hom.:

Bravo

AF:

0.0000227

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.64

CADD

Benign

0.75

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.081

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0016

LIST_S2

Benign

0.30

M_CAP

Benign

0.0051

MetaRNN

Benign

0.11

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-0.19

PhyloP100

-2.5

PrimateAI

Uncertain

0.52

PROVEAN

Benign

1.8

REVEL

Benign

0.15

Sift

Benign

0.59

Sift4G

Benign

0.29

Polyphen

1.0

Vest4

0.13

MutPred

0.38

Loss of methylation at K334 (P = 0.0112)

MVP

0.13

MPC

0.013

ClinPred

0.22

GERP RS

-6.6

Varity_R

0.096

gMVP

0.15

Mutation Taster

=99/1

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over