15-42638042-A-C

Variant names:

• chr15-42638042-A-C
• rs748650929
• NM_020759.3:c.401A>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_020759.3(STARD9):​c.401A>C​(p.Glu134Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E134G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: STARD9 NM_020759.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.44
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2704357).

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.401A>C	p.Glu134Ala	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.401A>C	p.Glu134Ala	missense	Exon 6 of 33	ENSP00000290607.7	Q9P2P6-1
	STARD9	ENST00000564158.5	TSL:1	n.458A>C		non_coding_transcript_exon	Exon 6 of 14
	STARD9	ENST00000563872.5	TSL:4	n.444A>C		non_coding_transcript_exon	Exon 6 of 6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.037	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	23
DANN	Benign	0.97
DEOGEN2	Benign	0.036	T
Eigen	Benign	-0.023
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.048	D
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.070	N
PhyloP100		4.4
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.24
Sift	Benign	0.049	D
Vest4		0.37
MutPred		0.64		Loss of stability (P = 0.0941)
MVP		0.53
ClinPred		0.54	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.12
gMVP		0.23
Mutation Taster		=67/33	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs748650929; hg19: chr15-42930240;