rs3742321

Variant names:

• chr13-33129928-T-C
• rs3742321
• NM_178006.4:c.749A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_178006.4(STARD13):​c.749A>G​(p.Lys250Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 1,613,144 control chromosomes in the GnomAD database, including 43,207 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. K250K) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.21 (3600 hom., cov: 32)
  • Exomes 𝑓: 0.23 (39607 hom.)
• Consequence: STARD13 NM_178006.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.27
• Publications: 28 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0013130903).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.269 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STARD13	NM_178006.4	c.749A>G	p.Lys250Arg	missense_variant	Exon 5 of 14	ENST00000336934.10	NP_821074.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STARD13	ENST00000336934.10	c.749A>G	p.Lys250Arg	missense_variant	Exon 5 of 14	1	NM_178006.4	ENSP00000338785.4
STARD13	ENST00000255486.8	c.725A>G	p.Lys242Arg	missense_variant	Exon 5 of 14	1		ENSP00000255486.4
STARD13	ENST00000567873.2	c.704A>G	p.Lys235Arg	missense_variant	Exon 5 of 14	1		ENSP00000456233.2
STARD13	ENST00000399365.7	c.395A>G	p.Lys132Arg	missense_variant	Exon 5 of 14	1		ENSP00000382300.3

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31433 AN: 152014 Hom.: 3595 Cov.: 32

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.284

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.221

Gnomad OTH AF: 0.205

GnomAD2 exomes AF: 0.242 AC: 60504 AN: 250254 AF XY: 0.242

Gnomad AFR exome AF: 0.123

Gnomad AMR exome AF: 0.322

Gnomad ASJ exome AF: 0.178

Gnomad EAS exome AF: 0.223

Gnomad FIN exome AF: 0.330

Gnomad NFE exome AF: 0.218

Gnomad OTH exome AF: 0.224

GnomAD4 exome AF: 0.229 AC: 335301 AN: 1461012 Hom.: 39607 Cov.: 47 AF XY: 0.230 AC XY: 167331 AN XY: 726808

African (AFR) AF: 0.125 AC: 4173 AN: 33478

American (AMR) AF: 0.317 AC: 14178 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 4621 AN: 26134

East Asian (EAS) AF: 0.234 AC: 9270 AN: 39700

South Asian (SAS) AF: 0.271 AC: 23392 AN: 86252

European-Finnish (FIN) AF: 0.328 AC: 17260 AN: 52674

Middle Eastern (MID) AF: 0.161 AC: 928 AN: 5768

European-Non Finnish (NFE) AF: 0.223 AC: 248272 AN: 1111906

Other (OTH) AF: 0.219 AC: 13207 AN: 60386

GnomAD4 genome AF: 0.207 AC: 31444 AN: 152132 Hom.: 3600 Cov.: 32 AF XY: 0.215 AC XY: 15950 AN XY: 74352

African (AFR) AF: 0.125 AC: 5200 AN: 41534

American (AMR) AF: 0.261 AC: 3994 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.156 AC: 540 AN: 3470

East Asian (EAS) AF: 0.221 AC: 1138 AN: 5146

South Asian (SAS) AF: 0.282 AC: 1357 AN: 4816

European-Finnish (FIN) AF: 0.344 AC: 3642 AN: 10590

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.221 AC: 14990 AN: 67970

Other (OTH) AF: 0.202 AC: 427 AN: 2114

Alfa AF: 0.213 Hom.: 12949

Bravo AF: 0.197

TwinsUK AF: 0.217 AC: 804

ALSPAC AF: 0.223 AC: 860

ESP6500AA AF: 0.131 AC: 575

ESP6500EA AF: 0.214 AC: 1839

ExAC AF: 0.237 AC: 28816

Asia WGS AF: 0.236 AC: 822 AN: 3478

EpiCase AF: 0.217

EpiControl AF: 0.219

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T;.;.;T
Eigen	Benign	0.0018
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.65	T;T;T;T
MetaRNN	Benign	0.0013	T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.4	M;.;.;.
PhyloP100		3.3
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-2.0	N;N;N;N
REVEL	Benign	0.093
Sift	Benign	0.045	D;D;D;T
Sift4G	Benign	0.073	T;T;T;.
Polyphen		0.044	B;B;.;.
Vest4		0.046
MPC		0.12
ClinPred		0.021	T
GERP RS		4.4
Varity_R		0.091
gMVP		0.17
Mutation Taster		=96/4	polymorphism (auto)

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: rs3742321; hg19: chr13-33704065; COSMIC: COSV55227395;