13-33112769-G-C

Position:

• chr13-33112769-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_178006.4(STARD13):​c.2444C>G​(p.Ala815Gly) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: STARD13 NM_178006.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.87

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.832

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STARD13	NM_178006.4	c.2444C>G	p.Ala815Gly	missense_variant	9/14	ENST00000336934.10	NP_821074.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STARD13	ENST00000336934.10	c.2444C>G	p.Ala815Gly	missense_variant	9/14	1	NM_178006.4	ENSP00000338785.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 07, 2024

The c.2444C>G (p.A815G) alteration is located in exon 9 (coding exon 9) of the STARD13 gene. This alteration results from a C to G substitution at nucleotide position 2444, causing the alanine (A) at amino acid position 815 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Uncertain	0.023	T
BayesDel_noAF	Benign	-0.20
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.30	T;.;.
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D;D;D
M_CAP	Benign	0.0079	T
MetaRNN	Pathogenic	0.83	D;D;D
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	1.1	L;.;.
PrimateAI	Pathogenic	0.80	T
PROVEAN	Uncertain	-3.5	D;D;D
REVEL	Uncertain	0.36
Sift	Benign	0.035	D;D;D
Sift4G	Uncertain	0.032	D;D;D
Polyphen		0.70	P;P;.
Vest4		0.79
MutPred		0.81		Loss of stability (P = 0.1576);.;.;
MVP		0.53
MPC		0.19
ClinPred		0.91	D
GERP RS		5.7
Varity_R		0.61
gMVP		0.51

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

Publications

LitVar

Other links and lift over

dbSNP: rs1566532439; hg19: chr13-33686906;