8-81693710-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001010893.3(SLC10A5):​c.1263G>T​(p.Lys421Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K421R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

SLC10A5
NM_001010893.3 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.549
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.15659901).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC10A5NM_001010893.3 linkc.1263G>T p.Lys421Asn 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.1263G>T p.Lys421Asn missense_variant Exon 1 of 1 6 NM_001010893.3 ENSP00000428612.1 Q5PT55

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Sep 29, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1263G>T (p.K421N) alteration is located in exon 1 (coding exon 1) of the SLC10A5 gene. This alteration results from a G to T substitution at nucleotide position 1263, causing the lysine (K) at amino acid position 421 to be replaced by an asparagine (N). 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
0.22
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Benign
-0.55
CADD
Benign
19
DANN
Uncertain
1.0
DEOGEN2
Benign
0.0062
T
Eigen
Benign
-0.20
Eigen_PC
Benign
-0.26
FATHMM_MKL
Benign
0.47
N
LIST_S2
Benign
0.48
T
M_CAP
Benign
0.0067
T
MetaRNN
Benign
0.16
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.2
M
PrimateAI
Benign
0.44
T
PROVEAN
Benign
-0.96
N
REVEL
Benign
0.10
Sift
Uncertain
0.0060
D
Sift4G
Uncertain
0.013
D
Polyphen
0.93
P
Vest4
0.21
MutPred
0.55
Gain of ubiquitination at K419 (P = 0.0477);
MVP
0.10
MPC
0.041
ClinPred
0.87
D
GERP RS
3.9
Varity_R
0.17
gMVP
0.16

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: chr8-82605945; API