chr10-59653830-G-C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_194298.3(SLC16A9):​c.1196C>G​(p.Ala399Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000248 in 1,613,948 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000025 ( 1 hom. )

Consequence

SLC16A9
NM_194298.3 missense

Scores

1
8
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.08

Publications

2 publications found
Variant links:
Genes affected
SLC16A9 (HGNC:23520): (solute carrier family 16 member 9) Predicted to enable monocarboxylic acid transmembrane transporter activity. Involved in urate metabolic process. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.762

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC16A9NM_194298.3 linkc.1196C>G p.Ala399Gly missense_variant Exon 5 of 6 ENST00000395348.8 NP_919274.1 Q7RTY1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC16A9ENST00000395348.8 linkc.1196C>G p.Ala399Gly missense_variant Exon 5 of 6 5 NM_194298.3 ENSP00000378757.3 Q7RTY1
SLC16A9ENST00000395347.1 linkc.1196C>G p.Ala399Gly missense_variant Exon 5 of 6 2 ENSP00000378756.1 Q7RTY1

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152080
Hom.:
0
Cov.:
32
show subpopulations
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:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.0000159
AC:
4
AN:
251418
AF XY:
0.0000147
show subpopulations
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:
0.0000352
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000253
AC:
37
AN:
1461868
Hom.:
1
Cov.:
33
AF XY:
0.0000206
AC XY:
15
AN XY:
727238
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33480
American (AMR)
AF:
0.00
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26134
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39690
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86256
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53418
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
0.0000315
AC:
35
AN:
1112004
Other (OTH)
AF:
0.0000331
AC:
2
AN:
60394
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.469
Heterozygous variant carriers
0
3
5
8
10
13
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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:
3
AN:
152080
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74286
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41410
American (AMR)
AF:
0.00
AC:
0
AN:
15274
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3470
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5176
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4816
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10616
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.0000441
AC:
3
AN:
68000
Other (OTH)
AF:
0.00
AC:
0
AN:
2090
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.508
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.0000227
ExAC
AF:
0.0000247
AC:
3
EpiCase
AF:
0.000164
EpiControl
AF:
0.0000593

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Apr 01, 2025
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.1196C>G (p.A399G) alteration is located in exon 5 (coding exon 4) of the SLC16A9 gene. This alteration results from a C to G substitution at nucleotide position 1196, causing the alanine (A) at amino acid position 399 to be replaced by a glycine (G). 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
0.16
BayesDel_addAF
Benign
-0.062
T
BayesDel_noAF
Benign
-0.20
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Benign
0.35
T;T
Eigen
Uncertain
0.51
Eigen_PC
Uncertain
0.43
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.87
.;D
M_CAP
Benign
0.045
D
MetaRNN
Pathogenic
0.76
D;D
MetaSVM
Benign
-0.51
T
MutationAssessor
Uncertain
2.5
M;M
PhyloP100
7.1
PrimateAI
Benign
0.46
T
PROVEAN
Uncertain
-2.7
D;D
REVEL
Uncertain
0.38
Sift
Benign
0.051
T;T
Sift4G
Benign
0.15
T;T
Polyphen
1.0
D;D
Vest4
0.60
MVP
0.41
MPC
0.56
ClinPred
0.85
D
GERP RS
5.2
Varity_R
0.44
gMVP
0.73
Mutation Taster
=52/48
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

Publications

Other links and lift over

dbSNP: rs750417619; hg19: chr10-61413588; API