7-44485002-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_015332.4(NUDCD3):​c.475G>C​(p.Ala159Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,414 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

NUDCD3
NM_015332.4 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.229
Variant links:
Genes affected
NUDCD3 (HGNC:22208): (NudC domain containing 3) The product of this gene functions to maintain the stability of dynein intermediate chain. Depletion of this gene product results in aggregation and degradation of dynein intermediate chain, mislocalization of the dynein complex from kinetochores, spindle microtubules, and spindle poles, and loss of gamma-tubulin from spindle poles. The protein localizes to the Golgi apparatus during interphase, and levels of the protein increase after the G1/S transition. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.06649175).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NUDCD3NM_015332.4 linkc.475G>C p.Ala159Pro missense_variant Exon 2 of 6 ENST00000355451.8 NP_056147.2 Q8IVD9
NUDCD3XM_011515247.3 linkc.475G>C p.Ala159Pro missense_variant Exon 2 of 6 XP_011513549.1
NUDCD3XM_017011908.2 linkc.475G>C p.Ala159Pro missense_variant Exon 2 of 4 XP_016867397.1
NUDCD3XR_007059994.1 linkn.533G>C non_coding_transcript_exon_variant Exon 2 of 5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NUDCD3ENST00000355451.8 linkc.475G>C p.Ala159Pro missense_variant Exon 2 of 6 1 NM_015332.4 ENSP00000347626.6 Q8IVD9
NUDCD3ENST00000464812.1 linkn.573G>C non_coding_transcript_exon_variant Exon 3 of 5 5
NUDCD3ENST00000480209.1 linkn.273G>C non_coding_transcript_exon_variant Exon 1 of 2 3
NUDCD3ENST00000497978.1 linkn.*67G>C downstream_gene_variant 4

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000120
AC:
3
AN:
250230
Hom.:
0
AF XY:
0.0000222
AC XY:
3
AN XY:
135294
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:
0.0000266
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000479
AC:
7
AN:
1461414
Hom.:
0
Cov.:
31
AF XY:
0.00000825
AC XY:
6
AN XY:
726958
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:
0.00000360
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.0000247
AC:
3
EpiCase
AF:
0.0000545
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
Dec 25, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.475G>C (p.A159P) alteration is located in exon 2 (coding exon 2) of the NUDCD3 gene. This alteration results from a G to C substitution at nucleotide position 475, causing the alanine (A) at amino acid position 159 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
Benign
0.081
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.55
CADD
Benign
12
DANN
Uncertain
0.99
DEOGEN2
Benign
0.0098
T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.23
N
LIST_S2
Benign
0.57
T
M_CAP
Benign
0.013
T
MetaRNN
Benign
0.066
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.8
L
PrimateAI
Benign
0.47
T
PROVEAN
Benign
0.33
N
REVEL
Benign
0.064
Sift
Benign
0.11
T
Sift4G
Uncertain
0.057
T
Polyphen
0.0
B
Vest4
0.16
MutPred
0.17
Loss of stability (P = 0.203);
MVP
0.26
MPC
0.76
ClinPred
0.28
T
GERP RS
-1.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.12
gMVP
0.21

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: rs753799747; hg19: chr7-44524601; API