Genetic Variant NUDT11:p.Leu23Leu (chrX-51496376-C-T) – ACMG Classification: Benign (-19 pts)

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_018159.4(NUDT11):c.69G>A(p.Leu23Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00283 in 1,207,342 control chromosomes in the GnomAD database, including 66 homozygotes. There are 911 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 46 hom., 402 hem., cov: 21)

Exomes 𝑓: 0.0016 ( 20 hom. 509 hem. )

Consequence

NUDT11
NM_018159.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.12

Variant links:

Genes affected

NUDT11 (HGNC:18011): (nudix hydrolase 11) NUDT11 belongs to a subgroup of phosphohydrolases that preferentially attack diphosphoinositol polyphosphates (Hidaka et al., 2002 [PubMed 12105228]).[supplied by OMIM, Mar 2008]

NUDT11 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.34).

BP6

Variant X-51496376-C-T is Benign according to our data. Variant chrX-51496376-C-T is described in ClinVar as [Benign]. Clinvar id is 790291.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.12 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0147 (1625/110458) while in subpopulation AFR AF= 0.0507 (1537/30288). AF 95% confidence interval is 0.0486. There are 46 homozygotes in gnomad4. There are 402 alleles in male gnomad4 subpopulation. Median coverage is 21. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 46 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUDT11	NM_018159.4 link	c.69G>A	p.Leu23Leu	synonymous_variant	Exon 1 of 2	ENST00000375992.4	NP_060629.2	Q96G61

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUDT11	ENST00000375992.4 link	c.69G>A	p.Leu23Leu	synonymous_variant	Exon 1 of 2	1	NM_018159.4	ENSP00000365160.3		Q96G61

Frequencies

GnomAD3 genomes

AF:

0.0147

AC:

1621

AN:

110404

Hom.:

Cov.:

AF XY:

0.0123

AC XY:

401

AN XY:

32620

show subpopulations

Gnomad AFR

AF:

0.0507

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00478

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00418

Gnomad NFE

AF:

0.000360

Gnomad OTH

AF:

0.0121

GnomAD3 exomes

AF:

0.00440

AC:

781

AN:

177679

Hom.:

AF XY:

0.00263

AC XY:

166

AN XY:

63059

show subpopulations

Gnomad AFR exome

AF:

0.0526

Gnomad AMR exome

AF:

0.00329

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000254

Gnomad OTH exome

AF:

0.00159

GnomAD4 exome

AF:

0.00163

AC:

1787

AN:

1096884

Hom.:

Cov.:

AF XY:

0.00140

AC XY:

509

AN XY:

362436

show subpopulations

Gnomad4 AFR exome

AF:

0.0506

Gnomad4 AMR exome

AF:

0.00359

Gnomad4 ASJ exome

AF:

0.0000517

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000223

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000166

Gnomad4 OTH exome

AF:

0.00361

GnomAD4 genome

AF:

0.0147

AC:

1625

AN:

110458

Hom.:

Cov.:

AF XY:

0.0123

AC XY:

402

AN XY:

32684

show subpopulations

Gnomad4 AFR

AF:

0.0507

Gnomad4 AMR

AF:

0.00478

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000360

Gnomad4 OTH

AF:

0.0120

Alfa

AF:

0.00740

Hom.:

Bravo

AF:

0.0170

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 23, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Uncertain

0.98

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over