rs150342077

Variant names:

• chr17-39653708-C-A
• rs150342077
• NM_006804.4:c.177C>A

Your query was ambiguous. Multiple possible variants found:

• chr17-39653708-C-A
• chr17-39653708-C-T

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_006804.4(STARD3):​c.177C>A​(p.Phe59Leu) 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 1,461,846 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. F59F) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: STARD3 NM_006804.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0700
• 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: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.955

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STARD3	NM_006804.4	c.177C>A	p.Phe59Leu	missense_variant	Exon 2 of 15	ENST00000336308.10	NP_006795.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STARD3	ENST00000336308.10	c.177C>A	p.Phe59Leu	missense_variant	Exon 2 of 15	1	NM_006804.4	ENSP00000337446.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461846 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727230

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

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: 26134

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53388

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

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112002

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

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.20
CADD	Uncertain	24
DANN	Benign	0.96
DEOGEN2	Uncertain	0.60	D;.;.;.;T;.;T;.;.;T;.
Eigen	Uncertain	0.22
Eigen_PC	Benign	0.042
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.93	D;D;D;D;D;D;D;D;D;D;D
M_CAP	Uncertain	0.22	D
MetaRNN	Pathogenic	0.95	D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.37	T
MutationAssessor	Pathogenic	3.1	M;M;.;M;.;.;.;.;.;.;.
PhyloP100		-0.070
PrimateAI	Pathogenic	0.85	D
PROVEAN	Pathogenic	-5.1	D;D;.;D;.;.;.;.;.;.;D
REVEL	Uncertain	0.63
Sift	Pathogenic	0.0	D;D;.;D;.;.;.;.;.;.;D
Sift4G	Pathogenic	0.0	D;D;D;D;D;D;D;D;D;D;D
Polyphen		1.0	D;.;.;.;.;.;.;.;.;.;.
Vest4		0.92
MutPred		0.92		Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);
MVP		0.66
MPC		1.2
ClinPred		1.0	D
GERP RS		0.45
Varity_R		0.89
gMVP		0.81

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.19		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: rs150342077; hg19: chr17-37809961;