11-72781124-C-T

Variant summary

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

The NM_006645.3(STARD10):​c.58G>A​(p.Glu20Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000731 in 1,613,672 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000078 ( 0 hom. )

Consequence

STARD10
NM_006645.3 missense

Scores

3
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.82
Variant links:
Genes affected
STARD10 (HGNC:10666): (StAR related lipid transfer domain containing 10) Predicted to enable lipid binding activity. Predicted to be involved in lipid transport. Predicted to act upstream of or within bile acid secretion and positive regulation of peroxisome proliferator activated receptor signaling pathway. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]
ARAP1 (HGNC:16925): (ArfGAP with RhoGAP domain, ankyrin repeat and PH domain 1) The protein encoded by this gene contains SAM, ARF-GAP, RHO-GAP, ankyrin repeat, RAS-associating, and pleckstrin homology (PH) domains. In vitro, this protein displays RHO-GAP and phosphatidylinositol (3,4,5) trisphosphate (PIP3)-dependent ARF-GAP activity. The encoded protein associates with the Golgi, and the ARF-GAP activity mediates changes in the Golgi and the formation of filopodia. It is thought to regulate the cell-specific trafficking of a receptor protein involved in apoptosis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2008]

Genome browser will be placed here

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=0.23059419).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
STARD10NM_006645.3 linkuse as main transcriptc.58G>A p.Glu20Lys missense_variant 2/7 ENST00000334805.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
STARD10ENST00000334805.11 linkuse as main transcriptc.58G>A p.Glu20Lys missense_variant 2/71 NM_006645.3 P1

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152236
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:
0.000478
GnomAD3 exomes
AF:
0.0000201
AC:
5
AN:
248906
Hom.:
0
AF XY:
0.0000222
AC XY:
3
AN XY:
135126
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 SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000442
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000780
AC:
114
AN:
1461436
Hom.:
0
Cov.:
31
AF XY:
0.0000798
AC XY:
58
AN XY:
727054
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:
0.000102
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152236
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74378
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.000478
Alfa
AF:
0.0000600
Hom.:
0
Bravo
AF:
0.0000189
ExAC
AF:
0.00000827
AC:
1
EpiCase
AF:
0.00
EpiControl
AF:
0.000119

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 GeneticsJan 10, 2023The c.58G>A (p.E20K) alteration is located in exon 2 (coding exon 1) of the STARD10 gene. This alteration results from a G to A substitution at nucleotide position 58, causing the glutamic acid (E) at amino acid position 20 to be replaced by a lysine (K). 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
0.24
BayesDel_addAF
Benign
-0.048
T
BayesDel_noAF
Benign
-0.18
CADD
Uncertain
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.033
T;T;T;T;T;.;.;.;T;T;T
Eigen
Benign
-0.19
Eigen_PC
Benign
-0.066
FATHMM_MKL
Uncertain
0.91
D
M_CAP
Benign
0.065
D
MetaRNN
Benign
0.23
T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.76
T
MutationTaster
Benign
0.91
N;N;N;N;D
PrimateAI
Uncertain
0.60
T
PROVEAN
Benign
-1.0
N;N;N;N;N;N;N;N;N;N;D
REVEL
Benign
0.094
Sift
Benign
0.034
D;D;T;D;T;T;T;D;T;T;D
Sift4G
Benign
0.11
T;T;T;T;.;T;.;T;.;T;.
Polyphen
0.010
B;B;B;.;.;.;.;.;.;.;.
Vest4
0.33
MutPred
0.44
Loss of helix (P = 0.0041);Loss of helix (P = 0.0041);Loss of helix (P = 0.0041);Loss of helix (P = 0.0041);Loss of helix (P = 0.0041);Loss of helix (P = 0.0041);Loss of helix (P = 0.0041);Loss of helix (P = 0.0041);Loss of helix (P = 0.0041);Loss of helix (P = 0.0041);Loss of helix (P = 0.0041);
MVP
0.81
MPC
0.61
ClinPred
0.35
T
GERP RS
3.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.34
gMVP
0.53

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs771499208; hg19: chr11-72492169; COSMIC: COSV105235866; COSMIC: COSV105235866; API