chr11-72755753-C-A

Variant names:

• chr11-72755753-C-A
• rs370159113
• NM_006645.3:c.578G>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_006645.3(STARD10):​c.578G>T​(p.Gly193Val) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,611,712 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. 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. G193A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: STARD10 NM_006645.3 missense, splice_region
• Scores: Splicing: ADA: 0.9990
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.73
• Publications: 1 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. Scorers claiming Benign: max_spliceai.

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.578G>T	p.Gly193Val	missense splice_region	Exon 6 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.578G>T	p.Gly193Val	missense splice_region	Exon 6 of 7	ENSP00000335247.6	Q9Y365
	STARD10	ENST00000543304.5	TSL:1	c.578G>T	p.Gly193Val	missense splice_region	Exon 7 of 8	ENSP00000438792.1	Q9Y365
	STARD10	ENST00000538536.5	TSL:1	c.440G>T	p.Gly147Val	missense splice_region	Exon 6 of 7	ENSP00000440016.1	F5GY11

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152152 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00110

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459560 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726056

African (AFR) AF: 0.00 AC: 0 AN: 33412

American (AMR) AF: 0.00 AC: 0 AN: 44484

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25998

East Asian (EAS) AF: 0.00 AC: 0 AN: 39634

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86014

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53248

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110734

Other (OTH) AF: 0.00 AC: 0 AN: 60282

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152152 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74320

African (AFR) AF: 0.00 AC: 0 AN: 41424

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68024

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

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.23
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.50	T
Eigen	Pathogenic	0.93
Eigen_PC	Pathogenic	0.85
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Uncertain	0.11	D
MetaRNN	Pathogenic	0.98	D
MetaSVM	Uncertain	0.38	D
PhyloP100		7.7
PrimateAI	Uncertain	0.72	T
PROVEAN	Pathogenic	-8.5	D
REVEL	Uncertain	0.58
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.99
MutPred		0.96		Gain of methylation at K192 (P = 0.0404)
MVP		0.75
MPC		1.6
ClinPred		1.0	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.91
gMVP		0.83
Mutation Taster		=12/88	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.89
SpliceAI score (max)		0.20		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.20		Position offset: 0

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs370159113; hg19: chr11-72466798;