Genetic Variant NUDCD3:p.Val236Phe (chr7-44404520-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_015332.4(NUDCD3):c.706G>T(p.Val236Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 152,004 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. V236I) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

NUDCD3
NM_015332.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.75

Publications

2 publications found

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]

NUDCD3 Gene-Disease associations (from GenCC):

severe combined immunodeficiency
Inheritance: AR Classification: LIMITED Submitted by: ClinGen

NUDCD3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015332.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUDCD3	NM_015332.4	MANE Select	c.706G>T	p.Val236Phe	missense	Exon 4 of 6	NP_056147.2	Q8IVD9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NUDCD3	ENST00000355451.8	TSL:1 MANE Select	c.706G>T	p.Val236Phe	missense	Exon 4 of 6	ENSP00000347626.6	Q8IVD9
NUDCD3	ENST00000460110.5	TSL:1	n.841G>T		non_coding_transcript_exon	Exon 5 of 7
NUDCD3	ENST00000873879.1		c.706G>T	p.Val236Phe	missense	Exon 4 of 7	ENSP00000543938.1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152004

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152004

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74248

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41376

American (AMR)

AF:

0.00

AC:

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4806

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67986

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.088

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.080

Eigen

Benign

0.16

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.84

M_CAP

Benign

0.0068

MetaRNN

Uncertain

0.63

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.6

PhyloP100

1.8

PrimateAI

Uncertain

0.49

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.17

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.043

Polyphen

0.17

Vest4

0.69

MutPred

0.57

Loss of disorder (P = 0.1228)

MVP

0.24

MPC

0.48

ClinPred

0.86

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.61

gMVP

0.61

Mutation Taster

=37/63

disease causing

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over