15-42637928-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_020759.3(STARD9):​c.373C>T​(p.Arg125Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000245 in 1,384,944 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

STARD9
NM_020759.3 missense

Scores

7
9
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.19
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.979

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
STARD9NM_020759.3 linkc.373C>T p.Arg125Trp missense_variant Exon 5 of 33 ENST00000290607.12 NP_065810.2 Q9P2P6-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
STARD9ENST00000290607.12 linkc.373C>T p.Arg125Trp missense_variant Exon 5 of 33 5 NM_020759.3 ENSP00000290607.7 Q9P2P6-1
STARD9ENST00000564158.5 linkn.430C>T non_coding_transcript_exon_variant Exon 5 of 14 1
STARD9ENST00000563872.5 linkn.416C>T non_coding_transcript_exon_variant Exon 5 of 6 4
STARD9ENST00000568493.1 linkn.444C>T non_coding_transcript_exon_variant Exon 3 of 11 2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000141
AC:
2
AN:
141906
Hom.:
0
AF XY:
0.0000263
AC XY:
2
AN XY:
75970
show subpopulations
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 SAS exome
AF:
0.0000440
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000245
AC:
34
AN:
1384944
Hom.:
0
Cov.:
31
AF XY:
0.0000234
AC XY:
16
AN XY:
683396
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000126
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000306
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Aug 21, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.373C>T (p.R125W) alteration is located in exon 5 (coding exon 5) of the STARD9 gene. This alteration results from a C to T substitution at nucleotide position 373, causing the arginine (R) at amino acid position 125 to be replaced by a tryptophan (W). 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
Pathogenic
0.58
BayesDel_addAF
Pathogenic
0.26
D
BayesDel_noAF
Uncertain
0.13
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.51
D
Eigen
Uncertain
0.34
Eigen_PC
Uncertain
0.32
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Pathogenic
0.99
D
M_CAP
Pathogenic
0.32
D
MetaRNN
Pathogenic
0.98
D
MetaSVM
Uncertain
0.67
D
MutationAssessor
Pathogenic
4.4
H
PrimateAI
Uncertain
0.70
T
PROVEAN
Pathogenic
-5.5
D
REVEL
Uncertain
0.62
Sift
Benign
0.046
D
Vest4
0.61
MutPred
0.91
Gain of catalytic residue at C127 (P = 0.2246);
MVP
0.75
ClinPred
0.94
D
GERP RS
4.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.29
gMVP
0.69

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.17
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1458784615; hg19: chr15-42930126; API