chr13-33106839-A-G

Variant names:

• chr13-33106839-A-G
• rs370325874
• NM_178006.4:c.3143T>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.3143T>C​(p.Val1048Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,856 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. V1048E) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: STARD13 NM_178006.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.50
• 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=0.2360312).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STARD13	NM_178006.4	c.3143T>C	p.Val1048Ala	missense_variant	Exon 13 of 14	ENST00000336934.10	NP_821074.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STARD13	ENST00000336934.10	c.3143T>C	p.Val1048Ala	missense_variant	Exon 13 of 14	1	NM_178006.4	ENSP00000338785.4
STARD13	ENST00000255486.8	c.3119T>C	p.Val1040Ala	missense_variant	Exon 13 of 14	1		ENSP00000255486.4
STARD13	ENST00000567873.2	c.3098T>C	p.Val1033Ala	missense_variant	Exon 13 of 14	1		ENSP00000456233.2
STARD13	ENST00000399365.7	c.2789T>C	p.Val930Ala	missense_variant	Exon 13 of 14	1		ENSP00000382300.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461856 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727234

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: 0.0000116 AC: 1 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: 0.00 AC: 0 AN: 1111974

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.076	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	15
DANN	Benign	0.79
DEOGEN2	Benign	0.21	T;.;.
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.55	D
LIST_S2	Benign	0.75	T;T;T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.24	T;T;T
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	1.6	L;.;.
PhyloP100		4.5
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.8	N;N;N
REVEL	Benign	0.22
Sift	Benign	0.46	T;T;T
Sift4G	Benign	0.67	T;T;T
Polyphen		0.0010	B;B;.
Vest4		0.37
MutPred		0.41		Loss of stability (P = 0.0421);.;.;
MVP		0.70
MPC		0.19
ClinPred		0.13	T
GERP RS		3.6
Varity_R		0.17
gMVP		0.34
Mutation Taster		=74/26	polymorphism

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: rs370325874; hg19: chr13-33680976;