Genetic Variant NM_020759.3:c.8030G>A (chr15-42689608-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_020759.3(STARD9):c.8030G>A(p.Arg2677His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 1,537,068 control chromosomes in the GnomAD database, including 64,581 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.39 ( 17536 hom., cov: 32)

Exomes 𝑓: 0.23 ( 47045 hom. )

Consequence

STARD9
NM_020759.3 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.77

Publications

22 publications found

Variant links:

Genes affected

STARD9 (HGNC:19162): (StAR related lipid transfer domain containing 9) Enables microtubule binding activity and microtubule motor activity. Involved in spindle assembly. Located in centriole; cytoplasm; and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

STARD9 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.2557972E-6).

BP6

Variant 15-42689608-G-A is Benign according to our data. Variant chr15-42689608-G-A is described in ClinVar as Benign. ClinVar VariationId is 3059971.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.826 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STARD9	NM_020759.3 link	c.8030G>A	p.Arg2677His	missense_variant	Exon 23 of 33	ENST00000290607.12	NP_065810.2	Q9P2P6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STARD9	ENST00000290607.12 link	c.8030G>A	p.Arg2677His	missense_variant	Exon 23 of 33	5	NM_020759.3	ENSP00000290607.7		Q9P2P6-1
STARD9	ENST00000562619.1 link	n.14G>A		non_coding_transcript_exon_variant	Exon 1 of 10	1		ENSP00000454648.1		H3BN21

Frequencies

GnomAD3 genomes

AF:

0.388

AC:

58933

AN:

151968

Hom.:

17478

Cov.:

show subpopulations

Gnomad AFR

AF:

0.833

Gnomad AMI

AF:

0.0923

Gnomad AMR

AF:

0.199

Gnomad ASJ

AF:

0.309

Gnomad EAS

AF:

0.229

Gnomad SAS

AF:

0.427

Gnomad FIN

AF:

0.236

Gnomad MID

AF:

0.256

Gnomad NFE

AF:

0.202

Gnomad OTH

AF:

0.335

GnomAD2 exomes

AF:

0.274

AC:

39065

AN:

142636

AF XY:

0.283

show subpopulations

Gnomad AFR exome

AF:

0.848

Gnomad AMR exome

AF:

0.128

Gnomad ASJ exome

AF:

0.306

Gnomad EAS exome

AF:

0.247

Gnomad FIN exome

AF:

0.236

Gnomad NFE exome

AF:

0.201

Gnomad OTH exome

AF:

0.248

GnomAD4 exome

AF:

0.233

AC:

322344

AN:

1384982

Hom.:

47045

Cov.:

AF XY:

0.238

AC XY:

162620

AN XY:

683430

show subpopulations

African (AFR)

AF:

0.860

AC:

27171

AN:

31592

American (AMR)

AF:

0.141

AC:

5039

AN:

35702

Ashkenazi Jewish (ASJ)

AF:

0.305

AC:

7673

AN:

25180

East Asian (EAS)

AF:

0.225

AC:

8042

AN:

35734

South Asian (SAS)

AF:

0.438

AC:

34723

AN:

79234

European-Finnish (FIN)

AF:

0.240

AC:

8420

AN:

35074

Middle Eastern (MID)

AF:

0.294

AC:

1675

AN:

5696

European-Non Finnish (NFE)

AF:

0.198

AC:

213738

AN:

1078790

Other (OTH)

AF:

0.274

AC:

15863

AN:

57980

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

13487

26974

40461

53948

67435

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7894

15788

23682

31576

39470

<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:

0.388

AC:

59048

AN:

152086

Hom.:

17536

Cov.:

AF XY:

0.385

AC XY:

28616

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.834

AC:

34592

AN:

41502

American (AMR)

AF:

0.199

AC:

3045

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.309

AC:

1073

AN:

3468

East Asian (EAS)

AF:

0.230

AC:

1185

AN:

5148

South Asian (SAS)

AF:

0.426

AC:

2052

AN:

4814

European-Finnish (FIN)

AF:

0.236

AC:

2494

AN:

10576

Middle Eastern (MID)

AF:

0.269

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.202

AC:

13742

AN:

67970

Other (OTH)

AF:

0.332

AC:

702

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1263

2525

3788

5050

6313

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

498

996

1494

1992

2490

<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:

0.258

Hom.:

32401

Bravo

AF:

0.399

TwinsUK

AF:

0.192

AC:

713

ALSPAC

AF:

0.195

AC:

750

ESP6500AA

AF:

0.827

AC:

1144

ESP6500EA

AF:

0.203

AC:

647

ExAC

AF:

0.347

AC:

8107

Asia WGS

AF:

0.351

AC:

1221

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

STARD9-related disorder

Benign:1

Oct 21, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.018

(source)

DANN

Benign

0.11

DEOGEN2

Benign

0.0022

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.00044

LIST_S2

Benign

0.32

MetaRNN

Benign

0.0000013

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.7

PhyloP100

-1.8

PrimateAI

Benign

0.29

PROVEAN

Benign

1.9

REVEL

Benign

0.041

Sift

Benign

1.0

Vest4

0.012

ClinPred

0.0075

GERP RS

-6.4

Varity_R

0.024

gMVP

0.053

Mutation Taster

=100/0

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over