chr8-109275381-G-T

Position:

• chr8-109275381-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032869.4(NUDCD1):​c.1144C>A​(p.Arg382Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,162 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: NUDCD1 NM_032869.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.86

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17532033).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUDCD1	NM_032869.4	c.1144C>A	p.Arg382Ser	missense_variant	7/10	ENST00000239690.9	NP_116258.2
NUDCD1	NM_001128211.2	c.1057C>A	p.Arg353Ser	missense_variant	7/10		NP_001121683.1
NUDCD1	XM_047422330.1	c.883C>A	p.Arg295Ser	missense_variant	7/10		XP_047278286.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUDCD1	ENST00000239690.9	c.1144C>A	p.Arg382Ser	missense_variant	7/10	1	NM_032869.4	ENSP00000239690	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461162 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726868

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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

Aug 07, 2023

The c.1144C>A (p.R382S) alteration is located in exon 7 (coding exon 7) of the NUDCD1 gene. This alteration results from a C to A substitution at nucleotide position 1144, causing the arginine (R) at amino acid position 382 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	Benign	0.24
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.044	T;.
Eigen	Benign	-0.13
Eigen_PC	Benign	0.019
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.81	T;T
M_CAP	Benign	0.0060	T
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	2.0	M;.
MutationTaster	Benign	0.56	D;N
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-3.4	D;D
REVEL	Benign	0.053
Sift	Benign	0.072	T;T
Sift4G	Benign	0.13	T;T
Polyphen		0.019	B;B
Vest4		0.29
MutPred		0.48		Loss of helix (P = 0.0076);.;
MVP		0.53
MPC		0.13
ClinPred		0.96	D
GERP RS		4.3
Varity_R		0.26
gMVP		0.65

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: rs377391733; hg19: chr8-110287610;