13-33106839-A-T

Variant names:

• chr13-33106839-A-T
• rs370325874
• NM_178006.4:c.3143T>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_178006.4(STARD13):​c.3143T>A​(p.Val1048Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000486 in 1,614,154 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00042 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00049 (5 hom.)
• Consequence: STARD13 NM_178006.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.50
• 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.016562372).
• BP6: Variant 13-33106839-A-T is Benign according to our data. Variant chr13-33106839-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 739620.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 5 Unknown gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STARD13	NM_178006.4	c.3143T>A	p.Val1048Glu	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>A	p.Val1048Glu	missense_variant	Exon 13 of 14	1	NM_178006.4	ENSP00000338785.4
STARD13	ENST00000255486.8	c.3119T>A	p.Val1040Glu	missense_variant	Exon 13 of 14	1		ENSP00000255486.4
STARD13	ENST00000567873.2	c.3098T>A	p.Val1033Glu	missense_variant	Exon 13 of 14	1		ENSP00000456233.2
STARD13	ENST00000399365.7	c.2789T>A	p.Val930Glu	missense_variant	Exon 13 of 14	1		ENSP00000382300.3

Frequencies

GnomAD3 genomes AF: 0.000421 AC: 64 AN: 152182 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0130

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000919 AC: 231 AN: 251232 AF XY: 0.00129

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000868

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000652

GnomAD4 exome AF: 0.000493 AC: 720 AN: 1461854 Hom.: 5 Cov.: 31 AF XY: 0.000712 AC XY: 518 AN XY: 727232

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.0000671 AC: 3 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: 0.00785 AC: 677 AN: 86256

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

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.00000630 AC: 7 AN: 1111974

Other (OTH) AF: 0.000513 AC: 31 AN: 60396

GnomAD4 genome AF: 0.000420 AC: 64 AN: 152300 Hom.: 0 Cov.: 32 AF XY: 0.000698 AC XY: 52 AN XY: 74464

African (AFR) AF: 0.0000241 AC: 1 AN: 41564

American (AMR) AF: 0.00 AC: 0 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.0131 AC: 63 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.0000838 Hom.: 0

Bravo AF: 0.0000567

ExAC AF: 0.00105 AC: 128

Asia WGS AF: 0.00837 AC: 29 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Apr 16, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.090
CADD	Benign	21
DANN	Benign	0.96
DEOGEN2	Benign	0.22	T;.;.
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.85	T;T;T
MetaRNN	Benign	0.017	T;T;T
MetaSVM	Benign	-0.54	T
MutationAssessor	Benign	1.6	L;.;.
PhyloP100		4.5
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-2.3	N;N;N
REVEL	Uncertain	0.50
Sift	Benign	0.19	T;T;T
Sift4G	Benign	0.37	T;T;T
Polyphen		0.37	B;B;.
Vest4		0.88
MutPred		0.58		Loss of stability (P = 0.0827);.;.;
MVP		0.86
MPC		0.61
ClinPred		0.12	T
GERP RS		3.6
Varity_R		0.40
gMVP		0.58
Mutation Taster		=72/28	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;