rs8030587

chr15-42689608-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_020759.3(STARD9):c.8030G>A(p.Arg2677His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 1,537,068 control chromosomes in the GnomAD database, including 64,581 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.39 (17536 hom., cov: 32)
  • Exomes 𝑓: 0.23 (47045 hom.)
• Consequence: STARD9 NM_020759.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.77

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.2557972E-6).
• BP6: Variant 15-42689608-G-A is Benign according to our data. Variant chr15-42689608-G-A is described in ClinVar as [Benign]. Clinvar id is 3059971.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.826 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STARD9	NM_020759.3	c.8030G>A	p.Arg2677His	missense_variant	23/33	ENST00000290607.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STARD9	ENST00000290607.12	c.8030G>A	p.Arg2677His	missense_variant	23/33	5	NM_020759.3	P1
STARD9	ENST00000562619.1	c.14G>A	p.Arg5His	missense_variant, NMD_transcript_variant	1/10	1

Frequencies

GnomAD3 genomes AF: 0.388 AC: 58933 AN: 151968 Hom.: 17478 Cov.: 32

Gnomad AFR AF: 0.833

Gnomad AMI AF: 0.0923

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.229

Gnomad SAS AF: 0.427

Gnomad FIN AF: 0.236

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.335

GnomAD3 exomes AF: 0.274 AC: 39065 AN: 142636 Hom.: 7421 AF XY: 0.283 AC XY: 21576 AN XY: 76134

Gnomad AFR exome AF: 0.848

Gnomad AMR exome AF: 0.128

Gnomad ASJ exome AF: 0.306

Gnomad EAS exome AF: 0.247

Gnomad SAS exome AF: 0.436

Gnomad FIN exome AF: 0.236

Gnomad NFE exome AF: 0.201

Gnomad OTH exome AF: 0.248

GnomAD4 exome AF: 0.233 AC: 322344 AN: 1384982 Hom.: 47045 Cov.: 37 AF XY: 0.238 AC XY: 162620 AN XY: 683430

Gnomad4 AFR exome AF: 0.860

Gnomad4 AMR exome AF: 0.141

Gnomad4 ASJ exome AF: 0.305

Gnomad4 EAS exome AF: 0.225

Gnomad4 SAS exome AF: 0.438

Gnomad4 FIN exome AF: 0.240

Gnomad4 NFE exome AF: 0.198

Gnomad4 OTH exome AF: 0.274

GnomAD4 genome AF: 0.388 AC: 59048 AN: 152086 Hom.: 17536 Cov.: 32 AF XY: 0.385 AC XY: 28616 AN XY: 74338

Gnomad4 AFR AF: 0.834

Gnomad4 AMR AF: 0.199

Gnomad4 ASJ AF: 0.309

Gnomad4 EAS AF: 0.230

Gnomad4 SAS AF: 0.426

Gnomad4 FIN AF: 0.236

Gnomad4 NFE AF: 0.202

Gnomad4 OTH AF: 0.332

Alfa AF: 0.232 Hom.: 11746

Bravo AF: 0.399

TwinsUK AF: 0.192 AC: 713

ALSPAC AF: 0.195 AC: 750

ESP6500AA AF: 0.827 AC: 1144

ESP6500EA AF: 0.203 AC: 647

ExAC AF: 0.347 AC: 8107

Asia WGS AF: 0.351 AC: 1221 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

STARD9-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 21, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.68
Cadd	Benign	0.018
Dann	Benign	0.11
DEOGEN2	Benign	0.0022	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.00044	N
LIST_S2	Benign	0.32	T
MetaRNN	Benign	0.0000013	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.7	N
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.29	T
PROVEAN	Benign	1.9	N
REVEL	Benign	0.041
Sift	Benign	1.0	T
Vest4		0.012
ClinPred		0.0075	T
GERP RS		-6.4
Varity_R		0.024
gMVP		0.053

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: rs8030587; hg19: chr15-42981806; COSMIC: COSV51899984;