NM_032869.4:c.1432G>C

Variant names:

• chr8-109245349-C-G
• NM_032869.4:c.1432G>C

Variant summary

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

The NM_032869.4(NUDCD1):​c.1432G>C​(p.Glu478Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NUDCD1 NM_032869.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.45

Genes affected

NUDCD1 (HGNC:24306): (NudC domain containing 1) Predicted to be involved in immune system process. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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
NUDCD1	NM_032869.4	c.1432G>C	p.Glu478Gln	missense_variant	Exon 9 of 10	ENST00000239690.9	NP_116258.2
NUDCD1	NM_001128211.2	c.1345G>C	p.Glu449Gln	missense_variant	Exon 9 of 10		NP_001121683.1
NUDCD1	XM_047422330.1	c.1171G>C	p.Glu391Gln	missense_variant	Exon 9 of 10		XP_047278286.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUDCD1	ENST00000239690.9	c.1432G>C	p.Glu478Gln	missense_variant	Exon 9 of 10	1	NM_032869.4	ENSP00000239690.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 08, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1432G>C (p.E478Q) alteration is located in exon 9 (coding exon 9) of the NUDCD1 gene. This alteration results from a G to C substitution at nucleotide position 1432, causing the glutamic acid (E) at amino acid position 478 to be replaced by a glutamine (Q). 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	0.13
BayesDel_addAF	Benign	-0.013	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0025	T;.
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.90	D;D
M_CAP	Benign	0.010	T
MetaRNN	Uncertain	0.57	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L;.
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.81	N;N
REVEL	Benign	0.15
Sift	Benign	0.11	T;T
Sift4G	Benign	0.28	T;T
Polyphen		0.51	P;P
Vest4		0.71
MutPred		0.29		Loss of catalytic residue at E478 (P = 0.147);.;
MVP		0.55
MPC		0.13
ClinPred		0.92	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.23
gMVP		0.35

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: chr8-110257578; COSMIC: COSV53459354;