17-39653708-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_006804.4(STARD3):c.177C>T(p.Phe59=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0011 in 1,614,220 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0010 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0011 (8 hom.)
• Consequence: STARD3 NM_006804.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0700

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

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 17-39653708-C-T is Benign according to our data. Variant chr17-39653708-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2647718.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.07 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STARD3	NM_006804.4	c.177C>T	p.Phe59=	synonymous_variant	2/15	ENST00000336308.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STARD3	ENST00000336308.10	c.177C>T	p.Phe59=	synonymous_variant	2/15	1	NM_006804.4	P1

Frequencies

GnomAD3 genomes AF: 0.00106 AC: 161 AN: 152256 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000654

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00228

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00169

Gnomad OTH AF: 0.00144

GnomAD3 exomes AF: 0.00148 AC: 372 AN: 251200 Hom.: 4 AF XY: 0.00171 AC XY: 232 AN XY: 135780

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.00124

Gnomad ASJ exome AF: 0.00397

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.00248

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.00171

Gnomad OTH exome AF: 0.00245

GnomAD4 exome AF: 0.00110 AC: 1614 AN: 1461846 Hom.: 8 Cov.: 31 AF XY: 0.00117 AC XY: 852 AN XY: 727230

Gnomad4 AFR exome AF: 0.000149

Gnomad4 AMR exome AF: 0.00123

Gnomad4 ASJ exome AF: 0.00310

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00234

Gnomad4 FIN exome AF: 0.0000375

Gnomad4 NFE exome AF: 0.000987

Gnomad4 OTH exome AF: 0.00184

GnomAD4 genome AF: 0.00104 AC: 159 AN: 152374 Hom.: 1 Cov.: 33 AF XY: 0.00111 AC XY: 83 AN XY: 74508

Gnomad4 AFR AF: 0.000192

Gnomad4 AMR AF: 0.000653

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00207

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.00169

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00152 Hom.: 1

Bravo AF: 0.00105

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00322

EpiControl AF: 0.00326

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2022

STARD3: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
Cadd	Benign	13
Dann	Benign	0.88

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

Publications

LitVar

Other links and lift over

dbSNP: rs150342077; hg19: chr17-37809961;