18-54597889-C-T

Variant summary

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

The NM_173629.3(DYNAP):​c.299C>T​(p.Thr100Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,380 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T100R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

DYNAP
NM_173629.3 missense

Scores

4
8
7

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.88
Variant links:
Genes affected
DYNAP (HGNC:26808): (dynactin associated protein) Involved in several processes, including activation of protein kinase B activity; cellular response to ergosterol; and positive regulation of cell population proliferation. Located in Golgi apparatus and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

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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
DYNAPNM_173629.3 linkc.299C>T p.Thr100Ile missense_variant Exon 3 of 3 ENST00000648945.2 NP_775900.2 Q8N1N2
DYNAPNM_001307955.1 linkc.221C>T p.Thr74Ile missense_variant Exon 3 of 3 NP_001294884.1 K7EMN5
DYNAPXM_011525923.4 linkc.386C>T p.Thr129Ile missense_variant Exon 5 of 5 XP_011524225.1
DYNAPXM_017025709.2 linkc.221C>T p.Thr74Ile missense_variant Exon 4 of 4 XP_016881198.1 K7EMN5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DYNAPENST00000648945.2 linkc.299C>T p.Thr100Ile missense_variant Exon 3 of 3 NM_173629.3 ENSP00000496812.1 A0A3B3IRJ4
DYNAPENST00000321600.1 linkc.377C>T p.Thr126Ile missense_variant Exon 3 of 3 2 ENSP00000315265.1 Q8N1N2
DYNAPENST00000585973.1 linkc.221C>T p.Thr74Ile missense_variant Exon 3 of 3 3 ENSP00000466577.1 K7EMN5

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461380
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
726962
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.00e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.49
BayesDel_addAF
Uncertain
0.032
T
BayesDel_noAF
Benign
-0.19
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.17
.;.;T
Eigen
Uncertain
0.54
Eigen_PC
Uncertain
0.46
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Benign
0.70
T;T;T
M_CAP
Benign
0.026
D
MetaRNN
Uncertain
0.62
D;D;D
MetaSVM
Benign
-0.89
T
MutationAssessor
Uncertain
2.0
.;.;M
PrimateAI
Uncertain
0.52
T
PROVEAN
Pathogenic
-5.8
.;.;D
REVEL
Benign
0.23
Sift
Pathogenic
0.0
.;.;D
Sift4G
Pathogenic
0.0
D;.;D
Polyphen
1.0
.;.;D
Vest4
0.50
MutPred
0.32
.;.;Loss of sheet (P = 0.1501);
MVP
0.28
MPC
0.099
ClinPred
1.0
D
GERP RS
4.8
Varity_R
0.92
gMVP
0.44

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: chr18-52265120; API