1-44806068-A-G

Variant summary

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

The NM_001377534.1(DYNLT4):​c.601T>C​(p.Ser201Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000742 in 1,602,932 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000074 ( 0 hom. )

Consequence

DYNLT4
NM_001377534.1 missense

Scores

2
11
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.35
Variant links:
Genes affected
DYNLT4 (HGNC:32315): (dynein light chain Tctex-type 4) Enables protein phosphatase 1 binding activity. Predicted to be involved in microtubule-based movement. Located in acrosomal vesicle; cytoskeleton; and sperm flagellum. [provided by Alliance of Genome Resources, Apr 2022]
PLK3 (HGNC:2154): (polo like kinase 3) The protein encoded by this gene is a member of the highly conserved polo-like kinase family of serine/threonine kinases. Members of this family are characterized by an amino-terminal kinase domain and a carboxy-terminal bipartite polo box domain that functions as a substrate-binding motif and a cellular localization signal. Polo-like kinases are important regulators of cell cycle progression. This gene has also been implicated in stress responses and double-strand break repair. In human cell lines, this protein is reported to associate with centrosomes in a microtubule-dependent manner, and during mitosis, the protein becomes localized to the mitotic apparatus. Expression of a kinase-defective mutant results in abnormal cell morphology caused by changes in microtubule dynamics and mitotic arrest followed by apoptosis. [provided by RefSeq, Sep 2015]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DYNLT4NM_001377534.1 linkc.601T>C p.Ser201Pro missense_variant Exon 3 of 3 ENST00000339355.3 NP_001364463.1
PLK3NM_004073.4 linkc.*390A>G downstream_gene_variant ENST00000372201.5 NP_004064.2 Q9H4B4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DYNLT4ENST00000339355.3 linkc.601T>C p.Ser201Pro missense_variant Exon 3 of 3 6 NM_001377534.1 ENSP00000341803.2 Q5JR98
PLK3ENST00000372201.5 linkc.*390A>G downstream_gene_variant 1 NM_004073.4 ENSP00000361275.4 Q9H4B4

Frequencies

GnomAD3 genomes
AF:
0.0000788
AC:
12
AN:
152220
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.00202
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000113
AC:
27
AN:
239542
Hom.:
0
AF XY:
0.0000916
AC XY:
12
AN XY:
131042
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000910
Gnomad ASJ exome
AF:
0.00178
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000652
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000738
AC:
107
AN:
1450712
Hom.:
0
Cov.:
31
AF XY:
0.0000680
AC XY:
49
AN XY:
720326
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000694
Gnomad4 ASJ exome
AF:
0.00206
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000586
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000289
Gnomad4 OTH exome
AF:
0.000234
GnomAD4 genome
AF:
0.0000788
AC:
12
AN:
152220
Hom.:
0
Cov.:
33
AF XY:
0.0000538
AC XY:
4
AN XY:
74368
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00202
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000167
Hom.:
0
Bravo
AF:
0.0000680
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000259
AC:
1
ExAC
AF:
0.0000908
AC:
11
Asia WGS
AF:
0.000289
AC:
2
AN:
3478
EpiCase
AF:
0.000382
EpiControl
AF:
0.000119

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jun 27, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.601T>C (p.S201P) alteration is located in exon 2 (coding exon 1) of the TCTEX1D4 gene. This alteration results from a T to C substitution at nucleotide position 601, causing the serine (S) at amino acid position 201 to be replaced by a proline (P). 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
0.73
BayesDel_addAF
Uncertain
0.11
D
BayesDel_noAF
Uncertain
0.13
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.25
T
Eigen
Uncertain
0.48
Eigen_PC
Uncertain
0.36
FATHMM_MKL
Benign
0.71
D
LIST_S2
Benign
0.44
T
M_CAP
Benign
0.069
D
MetaRNN
Uncertain
0.60
D
MetaSVM
Benign
-0.55
T
MutationAssessor
Pathogenic
3.5
H
PrimateAI
Uncertain
0.52
T
PROVEAN
Uncertain
-4.0
D
REVEL
Uncertain
0.43
Sift
Uncertain
0.0050
D
Sift4G
Uncertain
0.0060
D
Polyphen
0.99
D
Vest4
0.89
MVP
0.23
ClinPred
0.93
D
GERP RS
4.3
Varity_R
0.78
gMVP
0.73

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: rs201414613; hg19: chr1-45271740; API