13-33109945-C-G

Variant names:

• chr13-33109945-C-G
• rs528268102
• NM_178006.4:c.2975G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_178006.4(STARD13):​c.2975G>C​(p.Arg992Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign 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. R992K) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: STARD13 NM_178006.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.35
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21399704).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STARD13	NM_178006.4	c.2975G>C	p.Arg992Thr	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.2975G>C	p.Arg992Thr	missense_variant	Exon 12 of 14	1	NM_178006.4	ENSP00000338785.4
STARD13	ENST00000255486.8	c.2951G>C	p.Arg984Thr	missense_variant	Exon 12 of 14	1		ENSP00000255486.4
STARD13	ENST00000567873.2	c.2930G>C	p.Arg977Thr	missense_variant	Exon 12 of 14	1		ENSP00000456233.2
STARD13	ENST00000399365.7	c.2621G>C	p.Arg874Thr	missense_variant	Exon 12 of 14	1		ENSP00000382300.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	17
DANN	Benign	0.82
DEOGEN2	Benign	0.19	T;.;.
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.36
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Uncertain	0.94	D;D;D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.21	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.81	L;.;.
PhyloP100		1.3
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.5	N;N;N
REVEL	Benign	0.049
Sift	Benign	0.14	T;T;T
Sift4G	Benign	0.26	T;T;T
Polyphen		0.0010	B;B;.
Vest4		0.41
MutPred		0.30		Loss of helix (P = 0.079);.;.;
MVP		0.42
MPC		0.27
ClinPred		0.19	T
GERP RS		3.4
Varity_R		0.22
gMVP		0.21
Mutation Taster		=87/13	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs528268102; hg19: chr13-33684082;