rs8030587

Variant names:

• chr15-42689608-G-A
• rs8030587
• NM_020759.3:c.8030G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.39 (17536 hom., cov: 32)
  • Exomes 𝑓: 0.23 (47045 hom.)
• Consequence: STARD9 NM_020759.3 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -1.77
• Publications: 22 publications found

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

Our verdict: Benign. The variant received -13 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 VariationId is 3059971.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.826 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020759.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STARD9	NM_020759.3	MANE Select	c.8030G>A	p.Arg2677His	missense	Exon 23 of 33	NP_065810.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STARD9	ENST00000290607.12	TSL:5 MANE Select	c.8030G>A	p.Arg2677His	missense	Exon 23 of 33	ENSP00000290607.7
	STARD9	ENST00000562619.1	TSL:1	n.14G>A		non_coding_transcript_exon	Exon 1 of 10	ENSP00000454648.1

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

GnomAD2 exomes AF: 0.274 AC: 39065 AN: 142636 AF XY: 0.283

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 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

African (AFR) AF: 0.860 AC: 27171 AN: 31592

American (AMR) AF: 0.141 AC: 5039 AN: 35702

Ashkenazi Jewish (ASJ) AF: 0.305 AC: 7673 AN: 25180

East Asian (EAS) AF: 0.225 AC: 8042 AN: 35734

South Asian (SAS) AF: 0.438 AC: 34723 AN: 79234

European-Finnish (FIN) AF: 0.240 AC: 8420 AN: 35074

Middle Eastern (MID) AF: 0.294 AC: 1675 AN: 5696

European-Non Finnish (NFE) AF: 0.198 AC: 213738 AN: 1078790

Other (OTH) AF: 0.274 AC: 15863 AN: 57980

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

African (AFR) AF: 0.834 AC: 34592 AN: 41502

American (AMR) AF: 0.199 AC: 3045 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.309 AC: 1073 AN: 3468

East Asian (EAS) AF: 0.230 AC: 1185 AN: 5148

South Asian (SAS) AF: 0.426 AC: 2052 AN: 4814

European-Finnish (FIN) AF: 0.236 AC: 2494 AN: 10576

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.202 AC: 13742 AN: 67970

Other (OTH) AF: 0.332 AC: 702 AN: 2112

Alfa AF: 0.258 Hom.: 32401

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

ClinVar submissions as Germline

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	STARD9-related disorder (1)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		-1.8
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
Mutation Taster		=100/0	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: rs8030587; hg19: chr15-42981806; COSMIC: COSV51899984;