chr10-59654259-T-A

Variant summary

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

The NM_194298.3(SLC16A9):​c.767A>T​(p.Asn256Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000279 in 1,613,876 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 0.00014 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

SLC16A9
NM_194298.3 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.113

Publications

1 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: Likely_benign. The variant received -4 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.04534918).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC16A9NM_194298.3 linkc.767A>T p.Asn256Ile 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.767A>T p.Asn256Ile missense_variant Exon 5 of 6 5 NM_194298.3 ENSP00000378757.3 Q7RTY1
SLC16A9ENST00000395347.1 linkc.767A>T p.Asn256Ile missense_variant Exon 5 of 6 2 ENSP00000378756.1 Q7RTY1

Frequencies

GnomAD3 genomes
AF:
0.000145
AC:
22
AN:
152046
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
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:
0.0000239
AC:
6
AN:
251472
AF XY:
0.00000736
show subpopulations
Gnomad AFR exome
AF:
0.000369
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000157
AC:
23
AN:
1461830
Hom.:
0
Cov.:
34
AF XY:
0.0000124
AC XY:
9
AN XY:
727218
show subpopulations
African (AFR)
AF:
0.000627
AC:
21
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:
39692
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86250
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53412
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1111978
Other (OTH)
AF:
0.0000331
AC:
2
AN:
60392
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.471
Heterozygous variant carriers
0
1
3
4
6
7
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:
0.000145
AC:
22
AN:
152046
Hom.:
0
Cov.:
32
AF XY:
0.000148
AC XY:
11
AN XY:
74282
show subpopulations
African (AFR)
AF:
0.000483
AC:
20
AN:
41388
American (AMR)
AF:
0.0000655
AC:
1
AN:
15258
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3470
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5200
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4820
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10602
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.0000147
AC:
1
AN:
67996
Other (OTH)
AF:
0.00
AC:
0
AN:
2086
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.507
Heterozygous variant carriers
0
2
4
5
7
9
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome 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
Alfa
AF:
0.0000847
Hom.:
0
Bravo
AF:
0.000151
ESP6500AA
AF:
0.000454
AC:
2
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000165
AC:
2

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
May 28, 2024
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.767A>T (p.N256I) alteration is located in exon 5 (coding exon 4) of the SLC16A9 gene. This alteration results from a A to T substitution at nucleotide position 767, causing the asparagine (N) at amino acid position 256 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
Benign
0.071
BayesDel_addAF
Benign
-0.55
T
BayesDel_noAF
Benign
-0.68
CADD
Benign
0.23
DANN
Benign
0.88
DEOGEN2
Benign
0.099
T;T
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.32
N
LIST_S2
Benign
0.52
.;T
M_CAP
Benign
0.0036
T
MetaRNN
Benign
0.045
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.6
L;L
PhyloP100
0.11
PrimateAI
Benign
0.30
T
PROVEAN
Benign
-1.3
N;N
REVEL
Benign
0.12
Sift
Benign
0.14
T;T
Sift4G
Uncertain
0.035
D;D
Polyphen
0.27
B;B
Vest4
0.20
MVP
0.043
MPC
0.15
ClinPred
0.033
T
GERP RS
-1.0
Varity_R
0.11
gMVP
0.44
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

Publications

Other links and lift over

dbSNP: rs143605133; hg19: chr10-61414017; API