Genetic Variant STARD3:p.Arg14Leu (chr17-39653572-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006804.4(STARD3):c.41G>T(p.Arg14Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 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. R14H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

STARD3
NM_006804.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.745

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15233117).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STARD3	NM_006804.4 link	c.41G>T	p.Arg14Leu	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.41G>T	p.Arg14Leu	missense_variant	Exon 2 of 15	1	NM_006804.4	ENSP00000337446.5		Q14849-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1456248

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724722

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26124

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47890

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111966

Other (OTH)

AF:

0.00

AC:

AN:

60364

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

0.0067

BayesDel_noAF

Benign

-0.23

CADD

Benign

(source)

DANN

Benign

0.69

DEOGEN2

Benign

0.19

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

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.60

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.89

D;D;D;D;D;D;D;D;D;D;D

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.15

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

MetaSVM

Benign

-0.36

MutationAssessor

Uncertain

2.1

M;M;.;M;.;.;.;.;.;.;.

PhyloP100

0.74

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.9

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

REVEL

Benign

0.21

Sift

Benign

0.28

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

Sift4G

Benign

0.17

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

Polyphen

0.033

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

Vest4

0.44

MutPred

0.23

Loss of MoRF binding (P = 0.0107);Loss of MoRF binding (P = 0.0107);Loss of MoRF binding (P = 0.0107);Loss of MoRF binding (P = 0.0107);Loss of MoRF binding (P = 0.0107);Loss of MoRF binding (P = 0.0107);Loss of MoRF binding (P = 0.0107);Loss of MoRF binding (P = 0.0107);Loss of MoRF binding (P = 0.0107);Loss of MoRF binding (P = 0.0107);Loss of MoRF binding (P = 0.0107);

MVP

0.64

MPC

0.45

ClinPred

0.21

GERP RS

1.3

PromoterAI

0.015

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.060

gMVP

0.49

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over