chr15-42638054-C-T

Variant names:

• chr15-42638054-C-T
• rs763043649
• NM_020759.3:c.413C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_020759.3(STARD9):​c.413C>T​(p.Ala138Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000433 in 1,385,090 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000043 (0 hom.)
• Consequence: STARD9 NM_020759.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.63
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.15561554).

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.413C>T	p.Ala138Val	missense	Exon 6 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.413C>T	p.Ala138Val	missense	Exon 6 of 33	ENSP00000290607.7	Q9P2P6-1
	STARD9	ENST00000564158.5	TSL:1	n.470C>T		non_coding_transcript_exon	Exon 6 of 14
	STARD9	ENST00000563872.5	TSL:4	n.456C>T		non_coding_transcript_exon	Exon 6 of 6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000700 AC: 1 AN: 142924 AF XY: 0.0000131

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000174

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000433 AC: 6 AN: 1385090 Hom.: 0 Cov.: 31 AF XY: 0.00000439 AC XY: 3 AN XY: 683462

African (AFR) AF: 0.00 AC: 0 AN: 31590

American (AMR) AF: 0.00 AC: 0 AN: 35704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25182

East Asian (EAS) AF: 0.00 AC: 0 AN: 35736

South Asian (SAS) AF: 0.00 AC: 0 AN: 79234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35104

Middle Eastern (MID) AF: 0.000530 AC: 3 AN: 5660

European-Non Finnish (NFE) AF: 0.00000278 AC: 3 AN: 1078914

Other (OTH) AF: 0.00 AC: 0 AN: 57966

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000508 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000415 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.084	T
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.10
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.067	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	1.1	L
PhyloP100		2.6
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.10
Sift	Uncertain	0.0060	D
Vest4		0.24
MutPred		0.41		Loss of ubiquitination at K135 (P = 0.0714)
MVP		0.55
ClinPred		0.44	T
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.11
gMVP		0.056
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs763043649; hg19: chr15-42930252;