dbSNP rs199792176: STARD8:p.Arg184Gly (chrX-68717464-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001142503.3(STARD8):c.550C>G(p.Arg184Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000912 in 1,096,854 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R184W) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 22)

Exomes 𝑓: 9.1e-7 ( 0 hom. 0 hem. )

Consequence

STARD8
NM_001142503.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.820

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.060679942).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142503.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
STARD8	NM_001142503.3	MANE Select	c.550C>G	p.Arg184Gly	missense	Exon 6 of 15	NP_001135975.1	Q92502-2
STARD8	NM_001142504.3		c.310C>G	p.Arg104Gly	missense	Exon 5 of 14	NP_001135976.1	Q92502-1
STARD8	NM_014725.5		c.310C>G	p.Arg104Gly	missense	Exon 5 of 14	NP_055540.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
STARD8	ENST00000374599.8	TSL:1 MANE Select	c.550C>G	p.Arg184Gly	missense	Exon 6 of 15	ENSP00000363727.3	Q92502-2
STARD8	ENST00000252336.10	TSL:1	c.310C>G	p.Arg104Gly	missense	Exon 5 of 14	ENSP00000252336.6	Q92502-1
STARD8	ENST00000374597.3	TSL:1	c.310C>G	p.Arg104Gly	missense	Exon 5 of 14	ENSP00000363725.3	Q92502-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.12e-7

AC:

AN:

1096854

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

362458

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26400

American (AMR)

AF:

0.00

AC:

AN:

35167

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19351

East Asian (EAS)

AF:

0.00

AC:

AN:

30194

South Asian (SAS)

AF:

0.00

AC:

AN:

54090

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39656

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4132

European-Non Finnish (NFE)

AF:

0.00000119

AC:

AN:

841812

Other (OTH)

AF:

0.00

AC:

AN:

46052

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-1.0

CADD

Benign

4.8

(source)

DANN

Benign

0.53

DEOGEN2

Benign

0.0098

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.73

M_CAP

Benign

0.027

MetaRNN

Benign

0.061

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.2

PhyloP100

0.82

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.20

REVEL

Benign

0.011

Sift

Benign

0.41

Sift4G

Benign

0.51

Polyphen

0.0

Vest4

0.054

MutPred

0.16

Loss of stability (P = 0.064)

MVP

0.68

MPC

0.11

ClinPred

0.038

GERP RS

1.3

Varity_R

0.12

gMVP

0.19

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over