chrX-51496376-C-T

Variant names:

• chrX-51496376-C-T
• rs61729272
• NM_018159.4:c.69G>A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.12
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 21. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 46 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018159.4. 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
	NUDT11	NM_018159.4	MANE Select	c.69G>A	p.Leu23Leu	synonymous	Exon 1 of 2	NP_060629.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUDT11	ENST00000375992.4	TSL:1 MANE Select	c.69G>A	p.Leu23Leu	synonymous	Exon 1 of 2	ENSP00000365160.3	Q96G61

Frequencies

GnomAD3 genomes AF: 0.0147 AC: 1621 AN: 110404 Hom.: 46 Cov.: 21

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

GnomAD2 exomes AF: 0.00440 AC: 781 AN: 177679 AF XY: 0.00263

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 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.: 20 Cov.: 33 AF XY: 0.00140 AC XY: 509 AN XY: 362436

African (AFR) AF: 0.0506 AC: 1333 AN: 26369

American (AMR) AF: 0.00359 AC: 126 AN: 35097

Ashkenazi Jewish (ASJ) AF: 0.0000517 AC: 1 AN: 19333

East Asian (EAS) AF: 0.00 AC: 0 AN: 30177

South Asian (SAS) AF: 0.000223 AC: 12 AN: 53856

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40384

Middle Eastern (MID) AF: 0.00218 AC: 9 AN: 4132

European-Non Finnish (NFE) AF: 0.000166 AC: 140 AN: 841511

Other (OTH) AF: 0.00361 AC: 166 AN: 46025

GnomAD4 genome AF: 0.0147 AC: 1625 AN: 110458 Hom.: 46 Cov.: 21 AF XY: 0.0123 AC XY: 402 AN XY: 32684

African (AFR) AF: 0.0507 AC: 1537 AN: 30288

American (AMR) AF: 0.00478 AC: 50 AN: 10464

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2645

East Asian (EAS) AF: 0.00 AC: 0 AN: 3449

South Asian (SAS) AF: 0.00 AC: 0 AN: 2497

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5880

Middle Eastern (MID) AF: 0.00459 AC: 1 AN: 218

European-Non Finnish (NFE) AF: 0.000360 AC: 19 AN: 52843

Other (OTH) AF: 0.0120 AC: 18 AN: 1504

Alfa AF: 0.00740 Hom.: 45

Bravo AF: 0.0170

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	13
DANN	Uncertain	0.98
PhyloP100		1.1
PromoterAI		-0.033	Neutral

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: rs61729272; hg19: chrX-51239228;