Genetic Variant STARD8:p.Arg184Trp (chrX-68717464-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

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

The NM_001142503.3(STARD8):c.550C>T(p.Arg184Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000353 in 1,208,115 control chromosomes in the GnomAD database, including 1 homozygotes. There are 129 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00037 ( 0 hom., 12 hem., cov: 22)

Exomes 𝑓: 0.00035 ( 1 hom. 117 hem. )

Consequence

STARD8
NM_001142503.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.820

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]

STARD8 links:

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=0.02575615).

BS2

High Hemizygotes in GnomAd4 at 12 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STARD8	NM_001142503.3 link	c.550C>T	p.Arg184Trp	missense_variant	Exon 6 of 15	ENST00000374599.8	NP_001135975.1	Q92502-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STARD8	ENST00000374599.8 link	c.550C>T	p.Arg184Trp	missense_variant	Exon 6 of 15	1	NM_001142503.3	ENSP00000363727.3		Q92502-2

Frequencies

GnomAD3 genomes

AF:

0.000369

AC:

AN:

111211

Hom.:

Cov.:

AF XY:

0.000359

AC XY:

AN XY:

33415

show subpopulations

Gnomad AFR

AF:

0.0000983

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00114

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000472

Gnomad OTH

AF:

0.000664

GnomAD3 exomes

AF:

0.000216

AC:

AN:

180769

Hom.:

AF XY:

0.000167

AC XY:

AN XY:

65701

show subpopulations

Gnomad AFR exome

AF:

0.0000767

Gnomad AMR exome

AF:

0.000366

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000309

Gnomad OTH exome

AF:

0.000669

GnomAD4 exome

AF:

0.000351

AC:

385

AN:

1096850

Hom.:

Cov.:

AF XY:

0.000323

AC XY:

117

AN XY:

362454

show subpopulations

Gnomad4 AFR exome

AF:

0.000114

Gnomad4 AMR exome

AF:

0.000341

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000185

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000424

Gnomad4 OTH exome

AF:

0.000261

GnomAD4 genome

AF:

0.000368

AC:

AN:

111265

Hom.:

Cov.:

AF XY:

0.000358

AC XY:

AN XY:

33479

show subpopulations

Gnomad4 AFR

AF:

0.0000981

Gnomad4 AMR

AF:

0.00113

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000472

Gnomad4 OTH

AF:

0.000655

Alfa

AF:

0.00485

Hom.:

Bravo

AF:

0.000351

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.000189

AC:

EpiCase

AF:

0.000273

EpiControl

AF:

0.000416

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 27, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.550C>T (p.R184W) alteration is located in exon 6 (coding exon 6) of the STARD8 gene. This alteration results from a C to T substitution at nucleotide position 550, causing the arginine (R) at amino acid position 184 to be replaced by a tryptophan (W). 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

0.064

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.98

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.024

T;.;T

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.78

T;T;.

M_CAP

Benign

0.025

MetaRNN

Benign

0.026

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.83

L;.;L

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.8

N;N;N

REVEL

Benign

0.032

Sift

Benign

0.074

T;T;T

Sift4G

Benign

0.12

T;D;T

Polyphen

0.0

B;B;B

Vest4

0.064

MVP

0.73

MPC

0.064

ClinPred

0.029

GERP RS

1.3

Varity_R

0.083

gMVP

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over