17-39657035-G-A

Variant names:

• chr17-39657035-G-A
• rs142439753
• NM_006804.4:c.247G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006804.4(STARD3):​c.247G>A​(p.Glu83Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,868 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. 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. E83Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: STARD3 NM_006804.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.32
• Publications: 0 publications found

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]

ACMG classification

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=0.19338837).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STARD3	NM_006804.4	c.247G>A	p.Glu83Lys	missense_variant	Exon 3 of 15	ENST00000336308.10	NP_006795.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STARD3	ENST00000336308.10	c.247G>A	p.Glu83Lys	missense_variant	Exon 3 of 15	1	NM_006804.4	ENSP00000337446.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461868 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727232

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112004

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.097	T;.;.;.;T;.;.;.;T;.
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.085
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.89	D;D;D;D;D;D;D;D;D;D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.19	T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.48	N;N;.;N;.;.;.;.;.;.
PhyloP100		2.3
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-1.4	N;N;.;N;.;.;.;.;.;N
REVEL	Benign	0.077
Sift	Benign	0.69	T;T;.;T;.;.;.;.;.;T
Sift4G	Benign	0.49	T;T;T;T;T;T;T;T;T;T
Polyphen		0.012	B;.;.;.;.;.;.;.;.;.
Vest4		0.36
MutPred		0.61		Gain of methylation at E83 (P = 0.012);Gain of methylation at E83 (P = 0.012);Gain of methylation at E83 (P = 0.012);Gain of methylation at E83 (P = 0.012);Gain of methylation at E83 (P = 0.012);Gain of methylation at E83 (P = 0.012);Gain of methylation at E83 (P = 0.012);Gain of methylation at E83 (P = 0.012);Gain of methylation at E83 (P = 0.012);Gain of methylation at E83 (P = 0.012);
MVP		0.52
MPC		0.41
ClinPred		0.54	D
GERP RS		3.4
Varity_R		0.076
gMVP		0.58

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

Other links and lift over

dbSNP: rs142439753; hg19: chr17-37813288;