21-46161594-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001142854.2(SPATC1L):​c.808G>A​(p.Val270Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,458,056 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SPATC1L
NM_001142854.2 missense

Scores

5
13

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.464
Variant links:
Genes affected
SPATC1L (HGNC:1298): (spermatogenesis and centriole associated 1 like) Enables identical protein binding activity. Predicted to act upstream of or within several processes, including actin polymerization or depolymerization; positive regulation of cAMP-dependent protein kinase activity; and positive regulation of protein kinase A signaling. Predicted to be located in sperm connecting piece. Predicted to be active in centrosome. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.29520965).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SPATC1LNM_001142854.2 linkc.808G>A p.Val270Met missense_variant Exon 5 of 5 ENST00000291672.6 NP_001136326.1
SPATC1LNM_032261.5 linkc.346G>A p.Val116Met missense_variant Exon 4 of 4 NP_115637.3
SPATC1LXM_005261188.6 linkc.808G>A p.Val270Met missense_variant Exon 5 of 5 XP_005261245.1 Q9H0A9-1
SPATC1LXM_011529756.3 linkc.466G>A p.Val156Met missense_variant Exon 3 of 3 XP_011528058.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SPATC1LENST00000291672.6 linkc.808G>A p.Val270Met missense_variant Exon 5 of 5 2 NM_001142854.2 ENSP00000291672.5 Q9H0A9-1
SPATC1LENST00000330205.10 linkc.346G>A p.Val116Met missense_variant Exon 4 of 4 1 ENSP00000333869.6 Q9H0A9-2

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1458056
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
725182
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000194
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.30
BayesDel_addAF
Benign
-0.093
T
BayesDel_noAF
Benign
-0.37
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.012
.;T
Eigen
Uncertain
0.35
Eigen_PC
Uncertain
0.32
FATHMM_MKL
Benign
0.49
N
M_CAP
Benign
0.046
D
MetaRNN
Benign
0.30
T;T
MetaSVM
Benign
-0.88
T
MutationAssessor
Benign
1.3
.;L
PrimateAI
Uncertain
0.67
T
PROVEAN
Benign
-2.1
N;N
REVEL
Benign
0.14
Sift
Uncertain
0.029
D;D
Sift4G
Benign
0.085
T;T
Polyphen
1.0
.;D
Vest4
0.20
MutPred
0.43
.;Gain of disorder (P = 0.1081);
MVP
0.39
MPC
0.42
ClinPred
0.90
D
GERP RS
4.3
Varity_R
0.12
gMVP
0.60

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

LitVar

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

Other links and lift over

dbSNP: rs74518516; hg19: chr21-47581508; API