8-81693910-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001010893.3(SLC10A5):​c.1063G>C​(p.Ala355Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,768 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SLC10A5
NM_001010893.3 missense

Scores

6
8
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.26
Variant links:
Genes affected
SLC10A5 (HGNC:22981): (solute carrier family 10 member 5) Predicted to enable bile acid:sodium symporter activity. Predicted to be involved in bile acid and bile salt transport. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.897

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC10A5NM_001010893.3 linkc.1063G>C p.Ala355Pro missense_variant Exon 1 of 1 ENST00000518568.3 NP_001010893.1 Q5PT55

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC10A5ENST00000518568.3 linkc.1063G>C p.Ala355Pro missense_variant Exon 1 of 1 6 NM_001010893.3 ENSP00000428612.1 Q5PT55

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461768
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727180
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.:
32
Asia WGS
AF:
0.000577
AC:
2
AN:
3478

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Nov 18, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1063G>C (p.A355P) alteration is located in exon 1 (coding exon 1) of the SLC10A5 gene. This alteration results from a G to C substitution at nucleotide position 1063, causing the alanine (A) at amino acid position 355 to be replaced by a proline (P). 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
Uncertain
0.45
BayesDel_addAF
Pathogenic
0.35
D
BayesDel_noAF
Pathogenic
0.27
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.13
T
Eigen
Uncertain
0.37
Eigen_PC
Uncertain
0.27
FATHMM_MKL
Uncertain
0.89
D
LIST_S2
Benign
0.52
T
M_CAP
Benign
0.073
D
MetaRNN
Pathogenic
0.90
D
MetaSVM
Uncertain
0.083
D
MutationAssessor
Pathogenic
3.1
M
PrimateAI
Benign
0.42
T
PROVEAN
Pathogenic
-4.5
D
REVEL
Pathogenic
0.67
Sift
Uncertain
0.0020
D
Sift4G
Uncertain
0.020
D
Polyphen
0.99
D
Vest4
0.84
MutPred
0.70
Loss of catalytic residue at A355 (P = 0.0222);
MVP
0.82
MPC
0.036
ClinPred
0.90
D
GERP RS
2.5
Varity_R
0.70
gMVP
0.63

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.

Other links and lift over

dbSNP: rs374291519; hg19: chr8-82606145; API