chr13-33109888-T-G

Variant names:

• chr13-33109888-T-G
• rs144058395
• NM_178006.4:c.3032A>C

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_178006.4(STARD13):​c.3032A>C​(p.Asp1011Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,884 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 (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: STARD13 NM_178006.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.93
• Publications: 1 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: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.956

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STARD13	NM_178006.4	c.3032A>C	p.Asp1011Ala	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.3032A>C	p.Asp1011Ala	missense_variant	Exon 12 of 14	1	NM_178006.4	ENSP00000338785.4
STARD13	ENST00000255486.8	c.3008A>C	p.Asp1003Ala	missense_variant	Exon 12 of 14	1		ENSP00000255486.4
STARD13	ENST00000567873.2	c.2987A>C	p.Asp996Ala	missense_variant	Exon 12 of 14	1		ENSP00000456233.2
STARD13	ENST00000399365.7	c.2678A>C	p.Asp893Ala	missense_variant	Exon 12 of 14	1		ENSP00000382300.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251428 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461884 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727244

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1112002

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 13, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.3032A>C (p.D1011A) alteration is located in exon 12 (coding exon 12) of the STARD13 gene. This alteration results from a A to C substitution at nucleotide position 3032, causing the aspartic acid (D) at amino acid position 1011 to be replaced by an alanine (A). 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	Pathogenic	0.77
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.26
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.79	D;.;.
Eigen	Pathogenic	0.91
Eigen_PC	Pathogenic	0.88
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.98	D;D;D
M_CAP	Uncertain	0.11	D
MetaRNN	Pathogenic	0.96	D;D;D
MetaSVM	Uncertain	-0.0072	T
MutationAssessor	Pathogenic	3.0	M;.;.
PhyloP100		7.9
PrimateAI	Uncertain	0.65	T
PROVEAN	Pathogenic	-6.3	D;D;D
REVEL	Pathogenic	0.69
Sift	Uncertain	0.0020	D;D;D
Sift4G	Uncertain	0.0040	D;D;D
Polyphen		1.0	D;D;.
Vest4		0.95
MutPred		0.84		Gain of MoRF binding (P = 0.0229);.;.;
MVP		0.86
MPC		0.68
ClinPred		0.99	D
GERP RS		6.1
Varity_R		0.89
gMVP		0.81
Mutation Taster		=28/72	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs144058395; hg19: chr13-33684025;