rs774719913

Variant names:

• chr11-67629802-G-T
• rs774719913
• NM_001243750.2:c.110C>A

Your query was ambiguous. Multiple possible variants found:

• chr11-67629802-G-T
• chr11-67629802-G-A
• chr11-67629802-G-C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001243750.2(NUDT8):​c.110C>A​(p.Pro37Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000381 in 1,311,652 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000038 (0 hom.)
• Consequence: NUDT8 NM_001243750.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.99
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.771

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.110C>A	p.Pro37Gln	missense	Exon 1 of 4	NP_001230679.1	Q8WV74-1
	NUDT8	NM_181843.3		c.110C>A	p.Pro37Gln	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.110C>A	p.Pro37Gln	missense	Exon 1 of 4	ENSP00000365883.2	Q8WV74-1
	NUDT8	ENST00000301490.8	TSL:1	c.110C>A	p.Pro37Gln	missense	Exon 1 of 3	ENSP00000301490.4	Q8WV74-2
	NUDT8	ENST00000943310.1		c.110C>A	p.Pro37Gln	missense	Exon 1 of 5	ENSP00000613369.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000381 AC: 5 AN: 1311652 Hom.: 0 Cov.: 31 AF XY: 0.00000461 AC XY: 3 AN XY: 650796

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

African (AFR) AF: 0.0000367 AC: 1 AN: 27232

American (AMR) AF: 0.00 AC: 0 AN: 29162

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22360

East Asian (EAS) AF: 0.00 AC: 0 AN: 30816

South Asian (SAS) AF: 0.00 AC: 0 AN: 67490

European-Finnish (FIN) AF: 0.0000286 AC: 1 AN: 34924

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3772

European-Non Finnish (NFE) AF: 0.00000288 AC: 3 AN: 1042754

Other (OTH) AF: 0.00 AC: 0 AN: 53142

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000607163), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.93
BayesDel_addAF	Uncertain	0.020	T
BayesDel_noAF	Benign	-0.21
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Benign	0.21	T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Benign	0.23	N
LIST_S2	Uncertain	0.95	D
M_CAP	Pathogenic	0.71	D
MetaRNN	Pathogenic	0.77	D
MetaSVM	Benign	-0.95	T
MutationAssessor	Pathogenic	3.4	M
PhyloP100		2.0
PrimateAI	Pathogenic	0.93	D
PROVEAN	Pathogenic	-4.9	D
REVEL	Benign	0.18
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.56
MutPred		0.61		Gain of sheet (P = 0.0344)
MVP		0.23
MPC		0.90
ClinPred		0.93	D
GERP RS		2.9
PromoterAI		-0.048	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.50
gMVP		0.35
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

dbSNP: rs774719913; hg19: chr11-67397273;