Genetic Variant STARD8:p.Pro2Arg (chrX-68647887-C-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001142503.3(STARD8):c.5C>G(p.Pro2Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000509 in 1,198,859 control chromosomes in the GnomAD database, including 1 homozygotes. There are 15 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00027 ( 0 hom., 10 hem., cov: 24)

Exomes 𝑓: 0.000028 ( 1 hom. 5 hem. )

Consequence

STARD8
NM_001142503.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.46

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06039855).

BS2

High Hemizygotes in GnomAd4 at 10 gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STARD8	NM_001142503.3	MANE Select	c.5C>G	p.Pro2Arg	missense	Exon 1 of 15	NP_001135975.1	Q92502-2
	STARD8	NM_014725.5		c.-154C>G		5_prime_UTR	Exon 1 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.5C>G	p.Pro2Arg	missense	Exon 1 of 15	ENSP00000363727.3	Q92502-2
STARD8	ENST00000252336.10	TSL:1	c.-154C>G		5_prime_UTR	Exon 1 of 14	ENSP00000252336.6	Q92502-1
STARD8	ENST00000523864.5	TSL:1	n.5C>G		non_coding_transcript_exon	Exon 1 of 14	ENSP00000428031.1	E5RFN7

Frequencies

GnomAD3 genomes

AF:

0.000274

AC:

AN:

113319

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000832

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000277

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:

0.00

Gnomad OTH

AF:

0.00130

GnomAD2 exomes

AF:

0.0000719

AC:

AN:

153052

AF XY:

0.0000207

show subpopulations

Gnomad AFR exome

AF:

0.00111

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000276

AC:

AN:

1085491

Hom.:

Cov.:

AF XY:

0.0000141

AC XY:

AN XY:

354733

show subpopulations

African (AFR)

AF:

0.000920

AC:

AN:

26077

American (AMR)

AF:

0.0000892

AC:

AN:

33616

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19106

East Asian (EAS)

AF:

0.00

AC:

AN:

29535

South Asian (SAS)

AF:

0.00

AC:

AN:

51926

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39488

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4116

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

835967

Other (OTH)

AF:

0.0000657

AC:

AN:

45660

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.416

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000273

AC:

AN:

113368

Hom.:

Cov.:

AF XY:

0.000282

AC XY:

AN XY:

35504

show subpopulations

African (AFR)

AF:

0.000830

AC:

AN:

31331

American (AMR)

AF:

0.000277

AC:

AN:

10831

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2660

East Asian (EAS)

AF:

0.00

AC:

AN:

3548

South Asian (SAS)

AF:

0.00

AC:

AN:

2820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6341

Middle Eastern (MID)

AF:

0.00

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53379

Other (OTH)

AF:

0.00128

AC:

AN:

1557

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.000329

ESP6500AA

AF:

0.000762

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000755

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.70

CADD

Uncertain

(source)

DANN

Uncertain

1.0

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.51

M_CAP

Benign

0.060

MetaRNN

Benign

0.060

MetaSVM

Benign

-1.1

PhyloP100

2.5

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-0.57

REVEL

Benign

0.085

Sift

Pathogenic

0.0

Polyphen

0.94

Vest4

0.42

MVP

0.25

MPC

0.079

ClinPred

0.21

GERP RS

4.1

PromoterAI

-0.055

Neutral

(source)

gMVP

0.27

Mutation Taster

=295/5

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over