X-68716397-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001142503.3(STARD8):​c.263C>T​(p.Ser88Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000306 in 1,208,471 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 12 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000063 ( 0 hom., 2 hem., cov: 23)
Exomes 𝑓: 0.000027 ( 0 hom. 10 hem. )

Consequence

STARD8
NM_001142503.3 missense

Scores

7
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.75
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 Likely_benign. Variant got -4 ACMG points.

BS2
High Hemizygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
STARD8NM_001142503.3 linkc.263C>T p.Ser88Leu 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.263C>T p.Ser88Leu missense_variant Exon 5 of 15 1 NM_001142503.3 ENSP00000363727.3 Q92502-2

Frequencies

GnomAD3 genomes
AF:
0.0000632
AC:
7
AN:
110843
Hom.:
0
Cov.:
23
AF XY:
0.0000605
AC XY:
2
AN XY:
33083
show subpopulations
Gnomad AFR
AF:
0.000197
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:
0.000171
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000437
AC:
8
AN:
182920
Hom.:
0
AF XY:
0.0000297
AC XY:
2
AN XY:
67394
show subpopulations
Gnomad AFR exome
AF:
0.000229
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000217
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000627
Gnomad NFE exome
AF:
0.0000122
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000273
AC:
30
AN:
1097628
Hom.:
0
Cov.:
30
AF XY:
0.0000275
AC XY:
10
AN XY:
362996
show subpopulations
Gnomad4 AFR exome
AF:
0.000379
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000994
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000247
Gnomad4 NFE exome
AF:
0.00000832
Gnomad4 OTH exome
AF:
0.000152
GnomAD4 genome
AF:
0.0000632
AC:
7
AN:
110843
Hom.:
0
Cov.:
23
AF XY:
0.0000605
AC XY:
2
AN XY:
33083
show subpopulations
Gnomad4 AFR
AF:
0.000197
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000171
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000422
Hom.:
0
Bravo
AF:
0.0000453
ESP6500AA
AF:
0.000261
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000494
AC:
6

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Dec 03, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.263C>T (p.S88L) alteration is located in exon 5 (coding exon 5) of the STARD8 gene. This alteration results from a C to T substitution at nucleotide position 263, causing the serine (S) at amino acid position 88 to be replaced by a leucine (L). 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
0.12
BayesDel_addAF
Benign
-0.30
T
BayesDel_noAF
Benign
-0.38
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Benign
0.13
T;.;T
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.92
D;D;.
M_CAP
Uncertain
0.14
D
MetaRNN
Uncertain
0.70
D;D;D
MetaSVM
Benign
-0.72
T
MutationAssessor
Uncertain
2.1
M;.;M
PrimateAI
Uncertain
0.63
T
PROVEAN
Benign
-2.1
N;N;N
REVEL
Benign
0.080
Sift
Benign
0.12
T;T;T
Sift4G
Benign
0.27
T;T;T
Polyphen
1.0
D;D;D
Vest4
0.68
MVP
0.67
MPC
0.27
ClinPred
0.24
T
GERP RS
3.8
Varity_R
0.27
gMVP
0.12

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: rs371260205; hg19: chrX-67936239; COSMIC: COSV52923858; API