chr5-169588549-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001329642.2(SPDL1):​c.-155C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,422 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

SPDL1
NM_001329642.2 5_prime_UTR_premature_start_codon_gain

Scores

1
8
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.03
Variant links:
Genes affected
SPDL1 (HGNC:26010): (spindle apparatus coiled-coil protein 1) This gene encodes a coiled-coil domain-containing protein that functions in mitotic spindle formation and chromosome segregation. The encoded protein plays a role in coordinating microtubule attachment by promoting recruitment of dynein proteins, and in mitotic checkpoint signaling. [provided by RefSeq, Jul 2016]

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ACMG classification

Classification made for transcript

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=0.21814963).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SPDL1NM_017785.5 linkc.133C>T p.Arg45Cys missense_variant Exon 2 of 12 ENST00000265295.9 NP_060255.3 Q96EA4-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SPDL1ENST00000265295.9 linkc.133C>T p.Arg45Cys missense_variant Exon 2 of 12 1 NM_017785.5 ENSP00000265295.4 Q96EA4-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000400
AC:
1
AN:
249876
Hom.:
0
AF XY:
0.00000740
AC XY:
1
AN XY:
135100
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:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000884
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1460422
Hom.:
0
Cov.:
30
AF XY:
0.00000275
AC XY:
2
AN XY:
726530
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:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000468
Hom.:
0

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Dec 24, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.133C>T (p.R45C) alteration is located in exon 2 (coding exon 1) of the SPDL1 gene. This alteration results from a C to T substitution at nucleotide position 133, causing the arginine (R) at amino acid position 45 to be replaced by a cysteine (C). 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
0.11
BayesDel_addAF
Benign
0.0080
T
BayesDel_noAF
Benign
-0.23
CADD
Pathogenic
33
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.12
T;T;T;.;T;T;T
Eigen
Uncertain
0.49
Eigen_PC
Uncertain
0.44
FATHMM_MKL
Uncertain
0.79
D
LIST_S2
Uncertain
0.91
D;D;D;D;D;D;D
M_CAP
Benign
0.044
D
MetaRNN
Benign
0.22
T;T;T;T;T;T;T
MetaSVM
Benign
-0.94
T
MutationAssessor
Uncertain
2.4
M;.;.;.;.;.;.
PrimateAI
Benign
0.34
T
PROVEAN
Uncertain
-4.3
D;D;D;.;D;D;D
REVEL
Benign
0.15
Sift
Uncertain
0.0020
D;D;D;.;D;D;D
Sift4G
Uncertain
0.0040
D;D;D;D;D;D;D
Polyphen
1.0
D;.;.;.;.;.;.
Vest4
0.43
MutPred
0.090
Loss of MoRF binding (P = 0.2614);Loss of MoRF binding (P = 0.2614);Loss of MoRF binding (P = 0.2614);Loss of MoRF binding (P = 0.2614);Loss of MoRF binding (P = 0.2614);Loss of MoRF binding (P = 0.2614);Loss of MoRF binding (P = 0.2614);
MVP
0.55
MPC
0.27
ClinPred
0.98
D
GERP RS
4.7
Varity_R
0.26
gMVP
0.23

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs1430747630; hg19: chr5-169015553; COSMIC: COSV54668774; COSMIC: COSV54668774; API