chr8-109245349-C-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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

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_032869.4. 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
	NUDCD1	NM_032869.4	MANE Select	c.1432G>C	p.Glu478Gln	missense	Exon 9 of 10	NP_116258.2	Q96RS6-1
	NUDCD1	NM_001128211.2		c.1345G>C	p.Glu449Gln	missense	Exon 9 of 10	NP_001121683.1	Q96RS6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUDCD1	ENST00000239690.9	TSL:1 MANE Select	c.1432G>C	p.Glu478Gln	missense	Exon 9 of 10	ENSP00000239690.4	Q96RS6-1
	NUDCD1	ENST00000427660.6	TSL:1	c.1345G>C	p.Glu449Gln	missense	Exon 9 of 10	ENSP00000410707.2	Q96RS6-2
	NUDCD1	ENST00000519607.5	TSL:1	n.*1197G>C		non_coding_transcript_exon	Exon 10 of 11	ENSP00000430095.1	E5RGX7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.010	T
MetaRNN	Uncertain	0.57	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PhyloP100		7.4
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.81	N
REVEL	Benign	0.15
Sift	Benign	0.11	T
Sift4G	Benign	0.28	T
Polyphen		0.51	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
Mutation Taster		=61/39	polymorphism

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

Other links and lift over

hg19: chr8-110257578; COSMIC: COSV53459354;