chr15-42692090-A-G

Position:

• chr15-42692090-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_020759.3(STARD9):​c.10512A>G​(p.Thr3504=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0209 in 1,537,146 control chromosomes in the GnomAD database, including 1,352 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.058 (584 hom., cov: 32)
  • Exomes 𝑓: 0.017 (768 hom.)
• Consequence: STARD9 NM_020759.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.249

Genes affected

STARD9 (HGNC:19162): (StAR related lipid transfer domain containing 9) Enables microtubule binding activity and microtubule motor activity. Involved in spindle assembly. Located in centriole; cytoplasm; and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP7: Synonymous conserved (PhyloP=-0.249 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.165 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STARD9	NM_020759.3	c.10512A>G	p.Thr3504=	synonymous_variant	23/33	ENST00000290607.12	NP_065810.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STARD9	ENST00000290607.12	c.10512A>G	p.Thr3504=	synonymous_variant	23/33	5	NM_020759.3	ENSP00000290607	P1
STARD9	ENST00000562619.1	c.2496A>G	p.Thr832=	synonymous_variant, NMD_transcript_variant	1/10	1		ENSP00000454648

Frequencies

GnomAD3 genomes AF: 0.0577 AC: 8776 AN: 152120 Hom.: 582 Cov.: 32

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0247

Gnomad ASJ AF: 0.0329

Gnomad EAS AF: 0.0581

Gnomad SAS AF: 0.0331

Gnomad FIN AF: 0.00499

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0105

Gnomad OTH AF: 0.0426

GnomAD3 exomes AF: 0.0291 AC: 4044 AN: 139172 Hom.: 179 AF XY: 0.0286 AC XY: 2133 AN XY: 74626

Gnomad AFR exome AF: 0.174

Gnomad AMR exome AF: 0.0127

Gnomad ASJ exome AF: 0.0332

Gnomad EAS exome AF: 0.0636

Gnomad SAS exome AF: 0.0345

Gnomad FIN exome AF: 0.00297

Gnomad NFE exome AF: 0.0101

Gnomad OTH exome AF: 0.0229

GnomAD4 exome AF: 0.0168 AC: 23296 AN: 1384908 Hom.: 768 Cov.: 36 AF XY: 0.0170 AC XY: 11634 AN XY: 683384

Gnomad4 AFR exome AF: 0.182

Gnomad4 AMR exome AF: 0.0146

Gnomad4 ASJ exome AF: 0.0356

Gnomad4 EAS exome AF: 0.0499

Gnomad4 SAS exome AF: 0.0348

Gnomad4 FIN exome AF: 0.00366

Gnomad4 NFE exome AF: 0.00918

Gnomad4 OTH exome AF: 0.0251

GnomAD4 genome AF: 0.0578 AC: 8798 AN: 152238 Hom.: 584 Cov.: 32 AF XY: 0.0564 AC XY: 4201 AN XY: 74450

Gnomad4 AFR AF: 0.168

Gnomad4 AMR AF: 0.0247

Gnomad4 ASJ AF: 0.0329

Gnomad4 EAS AF: 0.0582

Gnomad4 SAS AF: 0.0333

Gnomad4 FIN AF: 0.00499

Gnomad4 NFE AF: 0.0105

Gnomad4 OTH AF: 0.0427

Alfa AF: 0.0195 Hom.: 229

Bravo AF: 0.0636

Asia WGS AF: 0.0530 AC: 184 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.71
DANN	Benign	0.27

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: rs16957063; hg19: chr15-42984288;