11-63290403-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001039752.4(SLC22A10):ā€‹c.238G>Cā€‹(p.Asp80His) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,624 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 31)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

SLC22A10
NM_001039752.4 missense

Scores

3
7
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.03
Variant links:
Genes affected
SLC22A10 (HGNC:18057): (solute carrier family 22 member 10) Predicted to enable transmembrane transporter activity. Predicted to be involved in organic anion transport. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SLC22A10NM_001039752.4 linkuse as main transcriptc.238G>C p.Asp80His missense_variant 1/10 ENST00000332793.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SLC22A10ENST00000332793.11 linkuse as main transcriptc.238G>C p.Asp80His missense_variant 1/101 NM_001039752.4 P1Q63ZE4-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461624
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
727112
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31
EpiCase
AF:
0.00
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
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsAug 02, 2022The c.238G>C (p.D80H) alteration is located in exon 1 (coding exon 1) of the SLC22A10 gene. This alteration results from a G to C substitution at nucleotide position 238, causing the aspartic acid (D) at amino acid position 80 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
Pathogenic
0.61
BayesDel_addAF
Uncertain
0.040
T
BayesDel_noAF
Benign
-0.18
CADD
Benign
21
DANN
Uncertain
0.99
DEOGEN2
Benign
0.078
T;.
Eigen
Uncertain
0.33
Eigen_PC
Benign
0.085
FATHMM_MKL
Benign
0.73
D
LIST_S2
Uncertain
0.96
D;D
M_CAP
Benign
0.041
D
MetaRNN
Uncertain
0.56
D;D
MetaSVM
Benign
-0.31
T
MutationAssessor
Pathogenic
3.6
H;.
MutationTaster
Benign
1.0
D;D;N;N
PrimateAI
Benign
0.46
T
PROVEAN
Pathogenic
-6.5
D;D
REVEL
Benign
0.28
Sift
Uncertain
0.014
D;D
Sift4G
Uncertain
0.018
D;D
Polyphen
1.0
D;.
Vest4
0.48
MutPred
0.43
Gain of catalytic residue at D80 (P = 0.1087);.;
MVP
0.55
MPC
0.12
ClinPred
0.99
D
GERP RS
2.9
Varity_R
0.48
gMVP
0.69

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-63057875; API