17-39653634-C-G

Variant names:

• chr17-39653634-C-G
• rs768753466
• NM_006804.4:c.103C>G

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.103C>G​(p.His35Asp) 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. 16/22 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. H35Y) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: STARD3 NM_006804.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.19
• 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=0.08265996).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006804.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STARD3	NM_006804.4	MANE Select	c.103C>G	p.His35Asp	missense	Exon 2 of 15	NP_006795.3
	STARD3	NM_001165937.2		c.103C>G	p.His35Asp	missense	Exon 2 of 15	NP_001159409.1	Q14849-3
	STARD3	NM_001165938.2		c.103C>G	p.His35Asp	missense	Exon 2 of 14	NP_001159410.1	Q14849-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STARD3	ENST00000336308.10	TSL:1 MANE Select	c.103C>G	p.His35Asp	missense	Exon 2 of 15	ENSP00000337446.5	Q14849-1
	STARD3	ENST00000580611.5	TSL:5	c.103C>G	p.His35Asp	missense	Exon 2 of 14	ENSP00000463613.1	J3QLM1
	STARD3	ENST00000936728.1		c.103C>G	p.His35Asp	missense	Exon 2 of 15	ENSP00000606787.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.030	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	14
DANN	Benign	0.49
DEOGEN2	Benign	0.081	T
Eigen	Benign	-0.99
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.074	D
MetaRNN	Benign	0.083	T
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	1.7	L
PhyloP100		2.2
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.17
Sift	Benign	0.82	T
Sift4G	Benign	0.50	T
Polyphen		0.20	B
Vest4		0.44
MutPred		0.18		Gain of relative solvent accessibility (P = 0.0479)
MVP		0.67
MPC		0.51
ClinPred		0.12	T
GERP RS		2.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.16
gMVP		0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs768753466; hg19: chr17-37809887;