11-67629787-C-G

Variant names:

• chr11-67629787-C-G
• rs769952154
• NM_001243750.2:c.125G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001243750.2(NUDT8):​c.125G>C​(p.Arg42Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000729 in 1,371,292 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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. R42L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: NUDT8 NM_001243750.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.604
• Publications: 0 publications found

Genes affected

NUDT8 (HGNC:8055): (nudix hydrolase 8) Predicted to enable magnesium ion binding activity and manganese ion binding activity. Predicted to be involved in purine nucleoside bisphosphate catabolic process. Predicted to be located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12746164).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001243750.2. 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
	NUDT8	NM_001243750.2	MANE Select	c.125G>C	p.Arg42Pro	missense	Exon 1 of 4	NP_001230679.1	Q8WV74-1
	NUDT8	NM_181843.3		c.125G>C	p.Arg42Pro	missense	Exon 1 of 3	NP_862826.1	Q8WV74-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUDT8	ENST00000376693.3	TSL:2 MANE Select	c.125G>C	p.Arg42Pro	missense	Exon 1 of 4	ENSP00000365883.2	Q8WV74-1
	NUDT8	ENST00000301490.8	TSL:1	c.125G>C	p.Arg42Pro	missense	Exon 1 of 3	ENSP00000301490.4	Q8WV74-2
	NUDT8	ENST00000943310.1		c.125G>C	p.Arg42Pro	missense	Exon 1 of 5	ENSP00000613369.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.29e-7 AC: 1 AN: 1371292 Hom.: 0 Cov.: 31 AF XY: 0.00000147 AC XY: 1 AN XY: 682332

African (AFR) AF: 0.00 AC: 0 AN: 28412

American (AMR) AF: 0.00 AC: 0 AN: 35374

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24030

East Asian (EAS) AF: 0.00 AC: 0 AN: 31724

South Asian (SAS) AF: 0.00 AC: 0 AN: 78206

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37874

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4016

European-Non Finnish (NFE) AF: 9.30e-7 AC: 1 AN: 1075428

Other (OTH) AF: 0.00 AC: 0 AN: 56228

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.047	T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.058	N
LIST_S2	Uncertain	0.89	D
M_CAP	Pathogenic	0.32	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.33	N
PhyloP100		-0.60
PrimateAI	Pathogenic	0.94	D
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.093
Sift	Benign	0.098	T
Sift4G	Benign	0.30	T
Polyphen		0.14	B
Vest4		0.23
MutPred		0.48		Loss of MoRF binding (P = 0.0076)
MVP		0.12
MPC		0.40
ClinPred		0.52	D
GERP RS		2.0
PromoterAI		0.038	Neutral
Varity_R		0.43
gMVP		0.35
Mutation Taster		=90/10	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: rs769952154; hg19: chr11-67397258;