chr18-54331801-C-T
Position:
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_139171.2(STARD6):c.326G>A(p.Arg109Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000205 in 1,461,026 control chromosomes in the GnomAD database, including 1 homozygotes. 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: 0.000021 ( 1 hom. )
Consequence
STARD6
NM_139171.2 missense
NM_139171.2 missense
Scores
10
3
2
Clinical Significance
Conservation
PhyloP100: 3.99
Genes affected
STARD6 (HGNC:18066): (StAR related lipid transfer domain containing 6) Cholesterol homeostasis is regulated, at least in part, by sterol regulatory element (SRE)-binding proteins (e.g., SREBP1; MIM 184756) and by liver X receptors (e.g., LXRA; MIM 602423). Upon sterol depletion, LXRs are inactive and SREBPs are cleaved, after which they bind promoter SREs and activate genes involved in cholesterol biosynthesis and uptake. Sterol transport is mediated by vesicles or by soluble protein carriers, such as steroidogenic acute regulatory protein (STAR; MIM 600617). STAR is homologous to a family of proteins containing a 200- to 210-amino acid STAR-related lipid transfer (START) domain, including STARD6 (Soccio et al., 2002 [PubMed 12011452]).[supplied by OMIM, Mar 2008]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.988
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
STARD6 | NM_139171.2 | c.326G>A | p.Arg109Gln | missense_variant | 6/8 | ENST00000307844.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
STARD6 | ENST00000307844.4 | c.326G>A | p.Arg109Gln | missense_variant | 6/8 | 1 | NM_139171.2 | P2 | |
STARD6 | ENST00000686109.1 | c.359G>A | p.Arg120Gln | missense_variant | 7/9 | A2 | |||
STARD6 | ENST00000581310.5 | c.326G>A | p.Arg109Gln | missense_variant | 7/9 | 5 | P2 | ||
STARD6 | ENST00000689888.1 | c.*382G>A | 3_prime_UTR_variant, NMD_transcript_variant | 6/8 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251304Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135818
GnomAD3 exomes
AF:
AC:
5
AN:
251304
Hom.:
AF XY:
AC XY:
5
AN XY:
135818
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000205 AC: 30AN: 1461026Hom.: 1 Cov.: 29 AF XY: 0.0000248 AC XY: 18AN XY: 726764
GnomAD4 exome
AF:
AC:
30
AN:
1461026
Hom.:
Cov.:
29
AF XY:
AC XY:
18
AN XY:
726764
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
Alfa
AF:
Hom.:
Bravo
AF:
ExAC
AF:
AC:
2
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 submitter | clinical testing | Ambry Genetics | Oct 12, 2021 | The c.326G>A (p.R109Q) alteration is located in exon 4 (coding exon 4) of the STARD6 gene. This alteration results from a G to A substitution at nucleotide position 326, causing the arginine (R) at amino acid position 109 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
M;M
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
Sift4G
Pathogenic
D;D
Polyphen
D;D
Vest4
MutPred
Loss of stability (P = 0.1872);Loss of stability (P = 0.1872);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at