8-109281004-T-C

Position:

• chr8-109281004-T-C

Variant summary

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

The NM_032869.4(NUDCD1):​c.992A>G​(p.His331Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,196 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 6.9e-7 (0 hom.)
• Consequence: NUDCD1 NM_032869.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.931

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=0.098710984).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUDCD1	NM_032869.4	c.992A>G	p.His331Arg	missense_variant	6/10	ENST00000239690.9	NP_116258.2
NUDCD1	NM_001128211.2	c.905A>G	p.His302Arg	missense_variant	6/10		NP_001121683.1
NUDCD1	XM_047422330.1	c.731A>G	p.His244Arg	missense_variant	6/10		XP_047278286.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUDCD1	ENST00000239690.9	c.992A>G	p.His331Arg	missense_variant	6/10	1	NM_032869.4	ENSP00000239690	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455196 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 724324

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: 9.04e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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

Nov 08, 2022

The c.992A>G (p.H331R) alteration is located in exon 6 (coding exon 6) of the NUDCD1 gene. This alteration results from a A to G substitution at nucleotide position 992, causing the histidine (H) at amino acid position 331 to be replaced by an arginine (R). 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	0.10
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	16
DANN	Benign	0.59
DEOGEN2	Benign	0.0057	T;.
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.19
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.74	T;T
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.099	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M;.
MutationTaster	Benign	0.91	N;N
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-2.0	N;N
REVEL	Benign	0.040
Sift	Benign	0.68	T;T
Sift4G	Benign	0.067	T;T
Polyphen		0.0	B;B
Vest4		0.21
MutPred		0.36		Gain of phosphorylation at S334 (P = 0.0632);.;
MVP		0.15
MPC		0.13
ClinPred		0.10	T
GERP RS		2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.067
gMVP		0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr8-110293233;