15-42585527-A-T

Position:

• chr15-42585527-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020759.3(STARD9):​c.124A>T​(p.Asn42Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 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)
• Consequence: STARD9 NM_020759.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.927

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1341145).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STARD9	NM_020759.3	c.124A>T	p.Asn42Tyr	missense_variant	3/33	ENST00000290607.12	NP_065810.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STARD9	ENST00000290607.12	c.124A>T	p.Asn42Tyr	missense_variant	3/33	5	NM_020759.3	ENSP00000290607.7
STARD9	ENST00000564158.5	n.181A>T		non_coding_transcript_exon_variant	3/14	1
STARD9	ENST00000563872.5	n.170A>T		non_coding_transcript_exon_variant	3/6	4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 24, 2024

The c.124A>T (p.N42Y) alteration is located in exon 3 (coding exon 3) of the STARD9 gene. This alteration results from a A to T substitution at nucleotide position 124, causing the asparagine (N) at amino acid position 42 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.099	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.21	T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.056	N
LIST_S2	Benign	0.63	T
M_CAP	Uncertain	0.085	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.80	T
MutationAssessor	Uncertain	2.7	M
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.14
Sift	Uncertain	0.0050	D
Vest4		0.24
MutPred		0.42		Loss of disorder (P = 0.0383);
MVP		0.44
ClinPred		0.19	T
GERP RS		-1.3
Varity_R		0.062
gMVP		0.12

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-42877725;