chr13-33109901-G-T

Variant names:

• chr13-33109901-G-T
• rs200778829
• NM_178006.4:c.3019C>A

Variant summary

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

The NM_178006.4(STARD13):​c.3019C>A​(p.His1007Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 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. H1007Y) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: STARD13 NM_178006.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.89
• Publications: 0 publications found

Genes affected

STARD13 (HGNC:19164): (StAR related lipid transfer domain containing 13) This gene encodes a protein which contains an N-terminal sterile alpha motif (SAM) for protein-protein interactions, followed by an ATP/GTP-binding motif, a GTPase-activating protein (GAP) domain, and a C-terminal STAR-related lipid transfer (START) domain. It may be involved in regulation of cytoskeletal reorganization, cell proliferation, and cell motility, and acts as a tumor suppressor in hepatoma cells. The gene is located in a region of chromosome 13 that is associated with loss of heterozygosity in hepatocellular carcinomas. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Aug 2011]

STARD13 Gene-Disease associations (from GenCC):

• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

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, 0.899

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STARD13	NM_178006.4	c.3019C>A	p.His1007Asn	missense_variant	Exon 12 of 14	ENST00000336934.10	NP_821074.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STARD13	ENST00000336934.10	c.3019C>A	p.His1007Asn	missense_variant	Exon 12 of 14	1	NM_178006.4	ENSP00000338785.4
STARD13	ENST00000255486.8	c.2995C>A	p.His999Asn	missense_variant	Exon 12 of 14	1		ENSP00000255486.4
STARD13	ENST00000567873.2	c.2974C>A	p.His992Asn	missense_variant	Exon 12 of 14	1		ENSP00000456233.2
STARD13	ENST00000399365.7	c.2665C>A	p.His889Asn	missense_variant	Exon 12 of 14	1		ENSP00000382300.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.030
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.67	D;.;.
Eigen	Pathogenic	0.92
Eigen_PC	Pathogenic	0.91
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.91	D;D;D
M_CAP	Benign	0.045	D
MetaRNN	Pathogenic	0.90	D;D;D
MetaSVM	Uncertain	0.39	D
MutationAssessor	Uncertain	2.8	M;.;.
PhyloP100		9.9
PrimateAI	Uncertain	0.52	T
PROVEAN	Pathogenic	-5.4	D;D;D
REVEL	Uncertain	0.62
Sift	Uncertain	0.010	D;D;D
Sift4G	Benign	0.13	T;T;T
Polyphen		0.96	D;P;.
Vest4		0.89
MutPred		0.58		Loss of catalytic residue at H1007 (P = 0.0354);.;.;
MVP		0.88
MPC		0.56
ClinPred		0.99	D
GERP RS		5.9
Varity_R		0.64
gMVP		0.55
Mutation Taster		=48/52	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: rs200778829; hg19: chr13-33684038; COSMIC: COSV99716174; COSMIC: COSV99716174;