17-39653628-T-A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_006804.4(STARD3):c.97T>A(p.Ser33Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,613,602 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

STARD3
NM_006804.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.880

Publications

0 publications found

Variant links:

Genes affected

STARD3 (HGNC:17579): (StAR related lipid transfer domain containing 3) This gene encodes a member of a subfamily of lipid trafficking proteins that are characterized by a C-terminal steroidogenic acute regulatory domain and an N-terminal metastatic lymph node 64 domain. The encoded protein localizes to the membranes of late endosomes and may be involved in exporting cholesterol. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Oct 2009]

STARD3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.07258278).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STARD3	NM_006804.4 link	c.97T>A	p.Ser33Thr	missense_variant	Exon 2 of 15	ENST00000336308.10	NP_006795.3	Q14849-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STARD3	ENST00000336308.10 link	c.97T>A	p.Ser33Thr	missense_variant	Exon 2 of 15	1	NM_006804.4	ENSP00000337446.5		Q14849-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000796

AC:

AN:

251126

AF XY:

0.00000737

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461426

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727034

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52988

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111986

Other (OTH)

AF:

0.0000166

AC:

AN:

60386

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

AF:

0.0000197

AC:

AN:

152176

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41440

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.000578

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68018

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 05, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.97T>A (p.S33T) alteration is located in exon 2 (coding exon 1) of the STARD3 gene. This alteration results from a T to A substitution at nucleotide position 97, causing the serine (S) at amino acid position 33 to be replaced by a threonine (T). 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

0.079

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.25

CADD

Benign

7.9

(source)

DANN

Benign

0.64

DEOGEN2

Benign

0.072

T;.;.;.;T;.;T;.;.;T;.

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.56

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.82

T;T;T;T;T;T;T;T;T;T;T

M_CAP

Uncertain

0.087

MetaRNN

Benign

0.073

T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.35

MutationAssessor

Benign

1.9

L;L;.;L;.;.;.;.;.;.;.

PhyloP100

0.88

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.76

N;N;.;N;.;.;.;.;.;.;N

REVEL

Benign

0.21

Sift

Benign

0.31

T;T;.;T;.;.;.;.;.;.;T

Sift4G

Benign

0.47

T;T;T;T;T;T;T;T;T;T;T

Polyphen

0.084

B;.;.;.;.;.;.;.;.;.;.

Vest4

0.17

MutPred

0.094

Gain of glycosylation at S33 (P = 0.0252);Gain of glycosylation at S33 (P = 0.0252);Gain of glycosylation at S33 (P = 0.0252);Gain of glycosylation at S33 (P = 0.0252);Gain of glycosylation at S33 (P = 0.0252);Gain of glycosylation at S33 (P = 0.0252);Gain of glycosylation at S33 (P = 0.0252);Gain of glycosylation at S33 (P = 0.0252);Gain of glycosylation at S33 (P = 0.0252);Gain of glycosylation at S33 (P = 0.0252);Gain of glycosylation at S33 (P = 0.0252);

MVP

0.68

MPC

0.33

ClinPred

0.067

GERP RS

3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.098

gMVP

0.46

Mutation Taster

=81/19

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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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17-39653628-T-A

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