11-72755132-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_006645.3(STARD10):​c.641A>T​(p.Lys214Met) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,578 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: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

STARD10
NM_006645.3 missense

Scores

1
7
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.95
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.2852079).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
STARD10NM_006645.3 linkuse as main transcriptc.641A>T p.Lys214Met missense_variant 7/7 ENST00000334805.11 NP_006636.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
STARD10ENST00000334805.11 linkuse as main transcriptc.641A>T p.Lys214Met missense_variant 7/71 NM_006645.3 ENSP00000335247 P1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1460578
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
726484
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:
9.00e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

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 GeneticsMar 12, 2024The c.641A>T (p.K214M) alteration is located in exon 7 (coding exon 6) of the STARD10 gene. This alteration results from a A to T substitution at nucleotide position 641, causing the lysine (K) at amino acid position 214 to be replaced by a methionine (M). 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
0.77
BayesDel_addAF
Benign
-0.030
T
BayesDel_noAF
Uncertain
0.070
CADD
Pathogenic
32
DANN
Uncertain
1.0
Eigen
Uncertain
0.65
Eigen_PC
Uncertain
0.59
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Benign
0.24
T
M_CAP
Uncertain
0.094
D
MetaRNN
Benign
0.29
T
MetaSVM
Uncertain
0.36
D
MutationTaster
Benign
1.0
D;D;D;D;D
PROVEAN
Benign
-0.14
N
REVEL
Benign
0.18
Sift
Benign
0.43
T
MutPred
0.40
Gain of helix (P = 0.027);
MVP
0.63
ClinPred
0.98
D
GERP RS
4.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.8

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: rs1414929124; hg19: chr11-72466177; API