8-109280995-C-T

Variant names:

• chr8-109280995-C-T
• rs752305500
• NM_032869.4:c.1001G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_032869.4(NUDCD1):​c.1001G>A​(p.Ser334Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,445,200 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S334T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: NUDCD1 NM_032869.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.11
• 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.1001G>A	p.Ser334Asn	missense	Exon 6 of 10	NP_116258.2	Q96RS6-1
	NUDCD1	NM_001128211.2		c.914G>A	p.Ser305Asn	missense	Exon 6 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.1001G>A	p.Ser334Asn	missense	Exon 6 of 10	ENSP00000239690.4	Q96RS6-1
	NUDCD1	ENST00000427660.6	TSL:1	c.914G>A	p.Ser305Asn	missense	Exon 6 of 10	ENSP00000410707.2	Q96RS6-2
	NUDCD1	ENST00000519607.5	TSL:1	n.*766G>A		non_coding_transcript_exon	Exon 7 of 11	ENSP00000430095.1	E5RGX7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1445200 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 720112

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33150

American (AMR) AF: 0.00 AC: 0 AN: 44670

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25962

East Asian (EAS) AF: 0.00 AC: 0 AN: 39480

South Asian (SAS) AF: 0.00 AC: 0 AN: 85642

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53148

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5728

European-Non Finnish (NFE) AF: 0.00000182 AC: 2 AN: 1097640

Other (OTH) AF: 0.00 AC: 0 AN: 59780

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00666416), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.70
BayesDel_addAF	Benign	-0.048	T
BayesDel_noAF	Benign	-0.31
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T
Eigen	Pathogenic	0.80
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.039	D
MetaRNN	Uncertain	0.69	D
MetaSVM	Benign	-0.53	T
MutationAssessor	Pathogenic	3.5	H
PhyloP100		3.1
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-2.3	N
REVEL	Uncertain	0.35
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.027	D
Polyphen		1.0	D
Vest4		0.50
MutPred		0.80		Gain of ubiquitination at K339 (P = 0.068)
MVP		0.47
MPC		0.52
ClinPred		0.99	D
GERP RS		5.4
Varity_R		0.45
gMVP		0.69
Mutation Taster		=69/31	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

dbSNP: rs752305500; hg19: chr8-110293224;