8-109289782-A-T

Position:

• chr8-109289782-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032869.4(NUDCD1):​c.792T>A​(p.Asn264Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000719 in 1,390,962 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: NUDCD1 NM_032869.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.462

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]

NUDCD1 (HGNC:):

ACMG classification

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=0.018260568).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUDCD1	NM_032869.4	c.792T>A	p.Asn264Lys	missense_variant	5/10	ENST00000239690.9	NP_116258.2
NUDCD1	NM_001128211.2	c.705T>A	p.Asn235Lys	missense_variant	5/10		NP_001121683.1
NUDCD1	XM_047422330.1	c.531T>A	p.Asn177Lys	missense_variant	5/10		XP_047278286.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUDCD1	ENST00000239690.9	c.792T>A	p.Asn264Lys	missense_variant	5/10	1	NM_032869.4	ENSP00000239690.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.19e-7 AC: 1 AN: 1390962 Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0 AN XY: 695120

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.45e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 07, 2024

The c.792T>A (p.N264K) alteration is located in exon 5 (coding exon 5) of the NUDCD1 gene. This alteration results from a T to A substitution at nucleotide position 792, causing the asparagine (N) at amino acid position 264 to be replaced by a lysine (K). 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	0.078
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.2
DANN	Benign	0.39
DEOGEN2	Benign	0.0013	T;.
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.073	N
LIST_S2	Benign	0.58	T;T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.018	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.2	L;.
PrimateAI	Benign	0.34	T
PROVEAN	Benign	0.23	N;N
REVEL	Benign	0.039
Sift	Benign	0.89	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0	B;B
Vest4		0.053
MutPred		0.33		Gain of ubiquitination at N264 (P = 0.0048);.;
MVP		0.072
MPC		0.13
ClinPred		0.044	T
GERP RS		0.40
Varity_R		0.033
gMVP		0.17

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

Other links and lift over

dbSNP: rs1814662823; hg19: chr8-110302011;