rs754062872

Variant names:

• chr11-72759339-C-A
• rs754062872
• NM_006645.3:c.250G>T

Your query was ambiguous. Multiple possible variants found:

• chr11-72759339-C-A
• chr11-72759339-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_006645.3(STARD10):​c.250G>T​(p.Asp84Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000066 in 151,602 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D84N) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: STARD10 NM_006645.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.83
• Publications: 2 publications found

Genes affected

STARD10 (HGNC:10666): (StAR related lipid transfer domain containing 10) Predicted to enable lipid binding activity. Predicted to be involved in lipid transport. Predicted to act upstream of or within bile acid secretion and positive regulation of peroxisome proliferator activated receptor signaling pathway. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ARAP1 (HGNC:16925): (ArfGAP with RhoGAP domain, ankyrin repeat and PH domain 1) The protein encoded by this gene contains SAM, ARF-GAP, RHO-GAP, ankyrin repeat, RAS-associating, and pleckstrin homology (PH) domains. In vitro, this protein displays RHO-GAP and phosphatidylinositol (3,4,5) trisphosphate (PIP3)-dependent ARF-GAP activity. The encoded protein associates with the Golgi, and the ARF-GAP activity mediates changes in the Golgi and the formation of filopodia. It is thought to regulate the cell-specific trafficking of a receptor protein involved in apoptosis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.894

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006645.3. 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
	STARD10	NM_006645.3	MANE Select	c.250G>T	p.Asp84Tyr	missense	Exon 3 of 7	NP_006636.2	Q9Y365

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STARD10	ENST00000334805.11	TSL:1 MANE Select	c.250G>T	p.Asp84Tyr	missense	Exon 3 of 7	ENSP00000335247.6	Q9Y365
	STARD10	ENST00000543304.5	TSL:1	c.250G>T	p.Asp84Tyr	missense	Exon 4 of 8	ENSP00000438792.1	Q9Y365
	STARD10	ENST00000538536.5	TSL:1	c.112G>T	p.Asp38Tyr	missense	Exon 3 of 7	ENSP00000440016.1	F5GY11

Frequencies

GnomAD3 genomes AF: 0.00000660 AC: 1 AN: 151602 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000195

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000801 AC: 2 AN: 249602 AF XY: 0.00000739

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000111

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000660 AC: 1 AN: 151602 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74004

African (AFR) AF: 0.00 AC: 0 AN: 41216

American (AMR) AF: 0.00 AC: 0 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000195 AC: 1 AN: 5138

South Asian (SAS) AF: 0.00 AC: 0 AN: 4798

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10568

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 308

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67894

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions as Germline

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	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.41
CADD	Pathogenic	31
DANN	Uncertain	0.99
DEOGEN2	Benign	0.35	T
Eigen	Pathogenic	0.98
Eigen_PC	Pathogenic	0.93
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Uncertain	0.24	D
MetaRNN	Pathogenic	0.89	D
MetaSVM	Uncertain	0.75	D
PhyloP100		7.8
PrimateAI	Uncertain	0.78	T
PROVEAN	Pathogenic	-8.8	D
REVEL	Pathogenic	0.65
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.87
MutPred		0.70		Gain of phosphorylation at D84 (P = 0.1199)
MVP		0.95
MPC		1.6
ClinPred		1.0	D
GERP RS		5.8
PromoterAI		-0.021	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.97
gMVP		0.90
Mutation Taster		=16/84	disease causing

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

Other links and lift over

dbSNP: rs754062872; hg19: chr11-72470384;