chr17-39653570-G-T

Variant names:

• chr17-39653570-G-T
• rs527648918
• NM_006804.4:c.39G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006804.4(STARD3):​c.39G>T​(p.Glu13Asp) variant causes a missense change. The variant allele was found at a frequency of 0.000011 in 1,455,980 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000011 (1 hom.)
• Consequence: STARD3 NM_006804.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.22
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29393044).

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.39G>T	p.Glu13Asp	missense	Exon 2 of 15	NP_006795.3
	STARD3	NM_001165937.2		c.39G>T	p.Glu13Asp	missense	Exon 2 of 15	NP_001159409.1	Q14849-3
	STARD3	NM_001165938.2		c.39G>T	p.Glu13Asp	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.39G>T	p.Glu13Asp	missense	Exon 2 of 15	ENSP00000337446.5	Q14849-1
	STARD3	ENST00000580611.5	TSL:5	c.39G>T	p.Glu13Asp	missense	Exon 2 of 14	ENSP00000463613.1	J3QLM1
	STARD3	ENST00000936728.1		c.39G>T	p.Glu13Asp	missense	Exon 2 of 15	ENSP00000606787.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000243 AC: 6 AN: 247022 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: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000110 AC: 16 AN: 1455980 Hom.: 1 Cov.: 31 AF XY: 0.0000138 AC XY: 10 AN XY: 724606

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

American (AMR) AF: 0.00 AC: 0 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

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

South Asian (SAS) AF: 0.000139 AC: 12 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111968

Other (OTH) AF: 0.0000497 AC: 3 AN: 60356

GnomAD4 genome Cov.: 33

ExAC AF: 0.0000165 AC: 2

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	23
DANN	Benign	0.74
DEOGEN2	Benign	0.16	T
Eigen	Uncertain	0.20
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.065	D
MetaRNN	Benign	0.29	T
MetaSVM	Uncertain	0.19	D
MutationAssessor	Uncertain	2.3	M
PhyloP100		4.2
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-1.5	N
REVEL	Uncertain	0.32
Sift	Benign	0.051	T
Sift4G	Benign	0.16	T
Polyphen		0.86	P
Vest4		0.24
MutPred		0.079		Loss of helix (P = 0.0237)
MVP		0.80
MPC		0.79
ClinPred		0.27	T
GERP RS		4.5
PromoterAI		0.056	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.10
gMVP		0.48
Mutation Taster		=79/21	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		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: rs527648918; hg19: chr17-37809823;