chr17-39653571-C-T

Variant names:

• chr17-39653571-C-T
• rs765536882
• NM_006804.4:c.40C>T

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.40C>T​(p.Arg14Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000205 in 1,608,294 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000022 (0 hom.)
• Consequence: STARD3 NM_006804.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.18
• 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=0.18961063).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STARD3	NM_006804.4	c.40C>T	p.Arg14Cys	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.40C>T	p.Arg14Cys	missense_variant	Exon 2 of 15	1	NM_006804.4	ENSP00000337446.5

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152194 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000121 AC: 3 AN: 247036 AF XY: 0.0000149

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000553

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000220 AC: 32 AN: 1456100 Hom.: 0 Cov.: 31 AF XY: 0.0000166 AC XY: 12 AN XY: 724652

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

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

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86254

European-Finnish (FIN) AF: 0.000105 AC: 5 AN: 47766

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.0000216 AC: 24 AN: 1111958

Other (OTH) AF: 0.0000166 AC: 1 AN: 60356

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152194 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74350

African (AFR) AF: 0.00 AC: 0 AN: 41448

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000227 Hom.: 0

Bravo AF: 0.0000227

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Uncertain	0.065	T
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	23
DANN	Benign	0.74
DEOGEN2	Benign	0.22	T;.;.;.;T;.;T;.;.;T;.
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.57
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.81	T;T;T;T;T;T;T;T;T;T;T
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.19	T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Uncertain	-0.11	T
MutationAssessor	Uncertain	2.1	M;M;.;M;.;.;.;.;.;.;.
PhyloP100		2.2
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.8	N;N;.;N;.;.;.;.;.;.;N
REVEL	Uncertain	0.43
Sift	Benign	0.093	T;T;.;T;.;.;.;.;.;.;T
Sift4G	Uncertain	0.032	D;D;D;T;T;D;D;D;T;D;D
Polyphen		0.0010	B;.;.;.;.;.;.;.;.;.;.
Vest4		0.22
MVP		0.66
MPC		0.49
ClinPred		0.090	T
GERP RS		3.5
PromoterAI		-0.021	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.077
gMVP		0.48
Mutation Taster		=65/35	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs765536882; hg19: chr17-37809824;