Genetic Variant STARD8:p.His114Arg (chrX-68717255-A-G) – 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.341A>G(p.His114Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000175 in 1,202,735 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 82 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 0.000099 ( 0 hom., 1 hem., cov: 22)

Exomes 𝑓: 0.00018 ( 0 hom. 81 hem. )

Consequence

STARD8
NM_001142503.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.51

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=0.04130736).

BS2

High Hemizygotes in GnomAdExome4 at 81 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STARD8	NM_001142503.3 link	c.341A>G	p.His114Arg	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.341A>G	p.His114Arg	missense_variant	Exon 6 of 15	1	NM_001142503.3	ENSP00000363727.3		Q92502-2

Frequencies

GnomAD3 genomes

AF:

0.0000986

AC:

AN:

111547

Hom.:

Cov.:

AF XY:

0.0000296

AC XY:

AN XY:

33729

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000379

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000170

Gnomad OTH

AF:

0.000662

GnomAD3 exomes

AF:

0.000249

AC:

AN:

164905

Hom.:

AF XY:

0.000365

AC XY:

AN XY:

52027

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000385

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00110

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000236

Gnomad OTH exome

AF:

0.00120

GnomAD4 exome

AF:

0.000182

AC:

199

AN:

1091188

Hom.:

Cov.:

AF XY:

0.000227

AC XY:

AN XY:

357536

show subpopulations

Gnomad4 AFR exome

AF:

0.0000380

Gnomad4 AMR exome

AF:

0.0000290

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000779

Gnomad4 FIN exome

AF:

0.0000250

Gnomad4 NFE exome

AF:

0.000137

Gnomad4 OTH exome

AF:

0.000436

GnomAD4 genome

AF:

0.0000986

AC:

AN:

111547

Hom.:

Cov.:

AF XY:

0.0000296

AC XY:

AN XY:

33729

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000379

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000170

Gnomad4 OTH

AF:

0.000662

Alfa

AF:

0.000260

Hom.:

Bravo

AF:

0.000136

ExAC

AF:

0.000132

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 26, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.341A>G (p.H114R) alteration is located in exon 6 (coding exon 6) of the STARD8 gene. This alteration results from a A to G substitution at nucleotide position 341, causing the histidine (H) at amino acid position 114 to be replaced by an arginine (R). 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

-0.69

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.70

DANN

Benign

0.45

DEOGEN2

Benign

0.0064

T;.;T

FATHMM_MKL

Benign

0.034

LIST_S2

Benign

0.75

T;T;.

M_CAP

Benign

0.0028

MetaRNN

Benign

0.041

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

L;.;L

PrimateAI

Benign

0.34

PROVEAN

Benign

2.4

N;N;N

REVEL

Benign

0.044

Sift

Benign

0.41

T;T;T

Sift4G

Benign

0.57

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.090

MutPred

0.32

Gain of solvent accessibility (P = 0.0074);.;Gain of solvent accessibility (P = 0.0074);

MVP

0.84

MPC

0.074

ClinPred

0.025

GERP RS

0.34

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.049

gMVP

0.047

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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