17-39657827-G-A

Variant names:

• chr17-39657827-G-A
• rs1877031
• NM_006804.4:c.350G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006804.4(STARD3):​c.350G>A​(p.Arg117Gln) variant causes a missense change. The variant allele was found at a frequency of 0.64 in 1,613,930 control chromosomes in the GnomAD database, including 340,167 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.52 (23729 hom., cov: 32)
  • Exomes 𝑓: 0.65 (316438 hom.)
• Consequence: STARD3 NM_006804.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.80
• Publications: 90 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=4.5651027E-6).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STARD3	NM_006804.4	MANE Select	c.350G>A	p.Arg117Gln	missense	Exon 4 of 15	NP_006795.3
	STARD3	NM_001165937.2		c.350G>A	p.Arg117Gln	missense	Exon 4 of 15	NP_001159409.1
	STARD3	NM_001165938.2		c.350G>A	p.Arg117Gln	missense	Exon 4 of 14	NP_001159410.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STARD3	ENST00000336308.10	TSL:1 MANE Select	c.350G>A	p.Arg117Gln	missense	Exon 4 of 15	ENSP00000337446.5
	STARD3	ENST00000580611.5	TSL:5	c.272G>A	p.Arg91Gln	missense	Exon 3 of 14	ENSP00000463613.1
	STARD3	ENST00000544210.6	TSL:2	c.350G>A	p.Arg117Gln	missense	Exon 4 of 15	ENSP00000439869.2

Frequencies

GnomAD3 genomes AF: 0.523 AC: 79448 AN: 151986 Hom.: 23724 Cov.: 32

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.738

Gnomad AMR AF: 0.537

Gnomad ASJ AF: 0.683

Gnomad EAS AF: 0.417

Gnomad SAS AF: 0.705

Gnomad FIN AF: 0.692

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.657

Gnomad OTH AF: 0.553

GnomAD2 exomes AF: 0.617 AC: 155180 AN: 251318 AF XY: 0.636

Gnomad AFR exome AF: 0.220

Gnomad AMR exome AF: 0.584

Gnomad ASJ exome AF: 0.691

Gnomad EAS exome AF: 0.388

Gnomad FIN exome AF: 0.694

Gnomad NFE exome AF: 0.668

Gnomad OTH exome AF: 0.641

GnomAD4 exome AF: 0.652 AC: 953637 AN: 1461826 Hom.: 316438 Cov.: 73 AF XY: 0.657 AC XY: 477481 AN XY: 727224

African (AFR) AF: 0.219 AC: 7319 AN: 33480

American (AMR) AF: 0.579 AC: 25874 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.686 AC: 17937 AN: 26134

East Asian (EAS) AF: 0.461 AC: 18282 AN: 39696

South Asian (SAS) AF: 0.740 AC: 63859 AN: 86258

European-Finnish (FIN) AF: 0.686 AC: 36665 AN: 53414

Middle Eastern (MID) AF: 0.711 AC: 4102 AN: 5768

European-Non Finnish (NFE) AF: 0.667 AC: 741300 AN: 1111964

Other (OTH) AF: 0.634 AC: 38299 AN: 60394

GnomAD4 genome AF: 0.522 AC: 79466 AN: 152104 Hom.: 23729 Cov.: 32 AF XY: 0.524 AC XY: 38951 AN XY: 74346

African (AFR) AF: 0.225 AC: 9353 AN: 41492

American (AMR) AF: 0.537 AC: 8209 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.683 AC: 2370 AN: 3468

East Asian (EAS) AF: 0.417 AC: 2154 AN: 5168

South Asian (SAS) AF: 0.706 AC: 3408 AN: 4824

European-Finnish (FIN) AF: 0.692 AC: 7322 AN: 10582

Middle Eastern (MID) AF: 0.616 AC: 181 AN: 294

European-Non Finnish (NFE) AF: 0.657 AC: 44626 AN: 67970

Other (OTH) AF: 0.553 AC: 1171 AN: 2116

Alfa AF: 0.619 Hom.: 102775

Bravo AF: 0.496

TwinsUK AF: 0.662 AC: 2453

ALSPAC AF: 0.654 AC: 2520

ESP6500AA AF: 0.237 AC: 1043

ESP6500EA AF: 0.653 AC: 5613

ExAC AF: 0.614 AC: 74570

Asia WGS AF: 0.588 AC: 2042 AN: 3476

EpiCase AF: 0.675

EpiControl AF: 0.668

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	T
Eigen	Benign	0.035
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.83	T
MetaRNN	Benign	0.0000046	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	2.0	M
PhyloP100		3.8
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.16
Sift	Benign	0.24	T
Sift4G	Benign	0.065	T
Polyphen		0.13	B
Vest4		0.40
MPC		0.55
ClinPred		0.029	T
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.18
gMVP		0.70
Mutation Taster		=94/6	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1877031; hg19: chr17-37814080; COSMIC: COSV60419443; COSMIC: COSV60419443;