7-44386067-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_015332.4(NUDCD3):​c.1030G>A​(p.Gly344Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

NUDCD3
NM_015332.4 missense

Scores

12
4
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.59
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.776

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NUDCD3NM_015332.4 linkc.1030G>A p.Gly344Ser missense_variant Exon 6 of 6 ENST00000355451.8 NP_056147.2 Q8IVD9
NUDCD3XM_011515247.3 linkc.976-2311G>A intron_variant Intron 5 of 5 XP_011513549.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NUDCD3ENST00000355451.8 linkc.1030G>A p.Gly344Ser missense_variant Exon 6 of 6 1 NM_015332.4 ENSP00000347626.6 Q8IVD9

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Mar 16, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1030G>A (p.G344S) alteration is located in exon 6 (coding exon 6) of the NUDCD3 gene. This alteration results from a G to A substitution at nucleotide position 1030, causing the glycine (G) at amino acid position 344 to be replaced by a serine (S). 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
0.84
BayesDel_addAF
Pathogenic
0.36
D
BayesDel_noAF
Pathogenic
0.28
CADD
Pathogenic
27
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.22
T
Eigen
Pathogenic
0.93
Eigen_PC
Pathogenic
0.91
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.94
D
M_CAP
Benign
0.052
D
MetaRNN
Pathogenic
0.78
D
MetaSVM
Uncertain
0.013
D
MutationAssessor
Uncertain
2.8
M
PrimateAI
Pathogenic
0.84
D
PROVEAN
Pathogenic
-5.0
D
REVEL
Uncertain
0.54
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.79
MutPred
0.32
Gain of phosphorylation at G344 (P = 0.0357);
MVP
0.70
MPC
0.88
ClinPred
0.99
D
GERP RS
5.9
Varity_R
0.84
gMVP
0.83

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: chr7-44425666; API