X-68716414-C-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001142503.3(STARD8):​c.280C>A​(p.His94Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00001 in 1,097,822 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 22)
Exomes 𝑓: 0.000010 ( 0 hom. 3 hem. )

Consequence

STARD8
NM_001142503.3 missense

Scores

1
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.582
Variant links:
Genes affected
STARD8 (HGNC:19161): (StAR related lipid transfer domain containing 8) This gene encodes a member of a subfamily of Rho GTPase activating proteins that contain a steroidogenic acute regulatory protein related lipid transfer domain. The encoded protein localizes to focal adhesions and may be involved in regulating cell morphology. This protein may also function as a tumor suppressor. [provided by RefSeq, Mar 2010]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.06586197).
BS2
High Hemizygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
STARD8NM_001142503.3 linkc.280C>A p.His94Asn missense_variant Exon 5 of 15 ENST00000374599.8 NP_001135975.1 Q92502-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
STARD8ENST00000374599.8 linkc.280C>A p.His94Asn missense_variant Exon 5 of 15 1 NM_001142503.3 ENSP00000363727.3 Q92502-2

Frequencies

GnomAD3 genomes
Cov.:
22
GnomAD4 exome
AF:
0.0000100
AC:
11
AN:
1097822
Hom.:
0
Cov.:
30
AF XY:
0.00000826
AC XY:
3
AN XY:
363182
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:
0.00
Gnomad4 OTH exome
AF:
0.0000217
GnomAD4 genome
Cov.:
22

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Aug 30, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.280C>A (p.H94N) alteration is located in exon 5 (coding exon 5) of the STARD8 gene. This alteration results from a C to A substitution at nucleotide position 280, causing the histidine (H) at amino acid position 94 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
0.090
BayesDel_addAF
Benign
-0.38
T
BayesDel_noAF
Benign
-0.78
CADD
Benign
17
DANN
Benign
0.94
DEOGEN2
Benign
0.0071
T;.;T
FATHMM_MKL
Benign
0.12
N
LIST_S2
Benign
0.77
T;T;.
M_CAP
Benign
0.068
D
MetaRNN
Benign
0.066
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.3
L;.;L
PrimateAI
Uncertain
0.60
T
PROVEAN
Benign
0.030
N;N;N
REVEL
Benign
0.053
Sift
Benign
1.0
T;T;T
Sift4G
Benign
0.76
T;T;T
Polyphen
0.0020
B;B;B
Vest4
0.30
MutPred
0.34
Loss of sheet (P = 3e-04);.;Loss of sheet (P = 3e-04);
MVP
0.50
MPC
0.067
ClinPred
0.14
T
GERP RS
3.8
Varity_R
0.22
gMVP
0.11

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: rs972737201; hg19: chrX-67936256; COSMIC: COSV99366833; API