11-72755753-C-G

Variant summary

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

The NM_006645.3(STARD10):ā€‹c.578G>Cā€‹(p.Gly193Ala) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000949 in 1,611,712 control chromosomes in the GnomAD database, with no homozygous occurrence. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.00011 ( 0 hom., cov: 31)
Exomes š‘“: 0.000093 ( 0 hom. )

Consequence

STARD10
NM_006645.3 missense, splice_region

Scores

8
9
1
Splicing: ADA: 0.9995
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.73
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 2 ACMG points.

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

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
STARD10NM_006645.3 linkuse as main transcriptc.578G>C p.Gly193Ala missense_variant, splice_region_variant 6/7 ENST00000334805.11 NP_006636.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
STARD10ENST00000334805.11 linkuse as main transcriptc.578G>C p.Gly193Ala missense_variant, splice_region_variant 6/71 NM_006645.3 ENSP00000335247 P1

Frequencies

GnomAD3 genomes
AF:
0.000112
AC:
17
AN:
152152
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.00123
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000810
AC:
20
AN:
247048
Hom.:
0
AF XY:
0.0000969
AC XY:
13
AN XY:
134172
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000146
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.000372
Gnomad NFE exome
AF:
0.0000536
Gnomad OTH exome
AF:
0.000167
GnomAD4 exome
AF:
0.0000932
AC:
136
AN:
1459560
Hom.:
0
Cov.:
31
AF XY:
0.000106
AC XY:
77
AN XY:
726056
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000135
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.000526
Gnomad4 NFE exome
AF:
0.0000900
Gnomad4 OTH exome
AF:
0.0000332
GnomAD4 genome
AF:
0.000112
AC:
17
AN:
152152
Hom.:
0
Cov.:
31
AF XY:
0.000135
AC XY:
10
AN XY:
74320
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00123
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000416
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000121
AC:
1
ExAC
AF:
0.0000662
AC:
8
EpiCase
AF:
0.000109
EpiControl
AF:
0.00

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 GeneticsJun 04, 2024The c.578G>C (p.G193A) alteration is located in exon 6 (coding exon 5) of the STARD10 gene. This alteration results from a G to C substitution at nucleotide position 578, causing the glycine (G) at amino acid position 193 to be replaced by an alanine (A). 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
0.99
BayesDel_addAF
Uncertain
0.036
T
BayesDel_noAF
Uncertain
0.040
CADD
Pathogenic
33
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.51
D;D;D;T;D;D;T
Eigen
Pathogenic
0.93
Eigen_PC
Pathogenic
0.85
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Pathogenic
0.98
D;.;D;D;D;D;D
M_CAP
Uncertain
0.092
D
MetaRNN
Uncertain
0.69
D;D;D;D;D;D;D
MetaSVM
Uncertain
0.38
D
MutationTaster
Benign
1.0
D;D;D;D;D
PrimateAI
Uncertain
0.71
T
PROVEAN
Pathogenic
-5.7
D;D;D;D;D;D;D
REVEL
Uncertain
0.58
Sift
Pathogenic
0.0
D;D;D;D;D;D;D
Sift4G
Pathogenic
0.0
D;D;D;D;D;.;.
Polyphen
1.0
.;D;D;D;.;.;.
Vest4
0.98, 0.98, 0.98, 0.97
MVP
0.74
MPC
1.5
ClinPred
0.76
D
GERP RS
5.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.89
gMVP
0.76

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
1.0
dbscSNV1_RF
Pathogenic
0.87
SpliceAI score (max)
0.080
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: rs370159113; hg19: chr11-72466798; API