13-33110725-C-T

Position:

• chr13-33110725-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_178006.4(STARD13):​c.2790G>A​(p.Thr930Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00218 in 1,614,194 control chromosomes in the GnomAD database, including 56 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0091 (22 hom., cov: 33)
  • Exomes 𝑓: 0.0015 (34 hom.)
• Consequence: STARD13 NM_178006.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.62

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 Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 13-33110725-C-T is Benign according to our data. Variant chr13-33110725-C-T is described in ClinVar as [Benign]. Clinvar id is 786239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.62 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0091 (1386/152316) while in subpopulation AFR AF= 0.0299 (1244/41566). AF 95% confidence interval is 0.0285. There are 22 homozygotes in gnomad4. There are 641 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 22 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STARD13	NM_178006.4	c.2790G>A	p.Thr930Thr	synonymous_variant	11/14	ENST00000336934.10	NP_821074.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STARD13	ENST00000336934.10	c.2790G>A	p.Thr930Thr	synonymous_variant	11/14	1	NM_178006.4	ENSP00000338785.4
STARD13	ENST00000255486.8	c.2766G>A	p.Thr922Thr	synonymous_variant	11/14	1		ENSP00000255486.4
STARD13	ENST00000567873.2	c.2745G>A	p.Thr915Thr	synonymous_variant	11/14	1		ENSP00000456233.2
STARD13	ENST00000399365.7	c.2436G>A	p.Thr812Thr	synonymous_variant	11/14	1		ENSP00000382300.3

Frequencies

GnomAD3 genomes AF: 0.00910 AC: 1385 AN: 152198 Hom.: 22 Cov.: 33

Gnomad AFR AF: 0.0300

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00931

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.0115

GnomAD3 exomes AF: 0.00348 AC: 876 AN: 251422 Hom.: 12 AF XY: 0.00298 AC XY: 405 AN XY: 135886

Gnomad AFR exome AF: 0.0296

Gnomad AMR exome AF: 0.00295

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00839

Gnomad FIN exome AF: 0.000370

Gnomad NFE exome AF: 0.000176

Gnomad OTH exome AF: 0.00130

GnomAD4 exome AF: 0.00146 AC: 2131 AN: 1461878 Hom.: 34 Cov.: 32 AF XY: 0.00156 AC XY: 1138 AN XY: 727238

Gnomad4 AFR exome AF: 0.0279

Gnomad4 AMR exome AF: 0.00295

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00721

Gnomad4 FIN exome AF: 0.000412

Gnomad4 NFE exome AF: 0.000158

Gnomad4 OTH exome AF: 0.00369

GnomAD4 genome AF: 0.00910 AC: 1386 AN: 152316 Hom.: 22 Cov.: 33 AF XY: 0.00861 AC XY: 641 AN XY: 74476

Gnomad4 AFR AF: 0.0299

Gnomad4 AMR AF: 0.00392

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00952

Gnomad4 FIN AF: 0.000189

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.0113

Alfa AF: 0.00323 Hom.: 2

Bravo AF: 0.0101

Asia WGS AF: 0.0120 AC: 40 AN: 3478

EpiCase AF: 0.000545

EpiControl AF: 0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 30, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	1.1
DANN	Uncertain	0.98
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs35364312; hg19: chr13-33684862;