chr3-131349638-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001353026.2(NEK11):​c.1829C>T​(p.Ala610Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000601 in 1,614,054 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. A610A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00025 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000040 ( 0 hom. )

Consequence

NEK11
NM_001353026.2 missense

Scores

15

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.42
Variant links:
Genes affected
NEK11 (HGNC:18593): (NIMA related kinase 11) This gene encodes a member of the never in mitosis gene A family of kinases. The encoded protein localizes to the nucleoli, and may function with NEK2A in the S-phase checkpoint. The encoded protein appears to play roles in DNA replication and response to genotoxic stress. Alternatively spliced transcript variants have been described.[provided by RefSeq, Mar 2009]
NUDT16-DT (HGNC:27947): (NUDT16 divergent transcript)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.010293454).
BP6
Variant 3-131349638-C-T is Benign according to our data. Variant chr3-131349638-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3878732.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NEK11NM_024800.5 linkc.1800C>T p.Ser600Ser synonymous_variant Exon 18 of 18 ENST00000383366.9 NP_079076.3 Q8NG66-1B4DM56

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NEK11ENST00000383366.9 linkc.1800C>T p.Ser600Ser synonymous_variant Exon 18 of 18 1 NM_024800.5 ENSP00000372857.4 Q8NG66-1

Frequencies

GnomAD3 genomes
AF:
0.000250
AC:
38
AN:
152082
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000749
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0000943
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000796
AC:
20
AN:
251214
Hom.:
0
AF XY:
0.0000810
AC XY:
11
AN XY:
135758
show subpopulations
Gnomad AFR exome
AF:
0.000738
Gnomad AMR exome
AF:
0.0000868
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000264
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000404
AC:
59
AN:
1461856
Hom.:
0
Cov.:
31
AF XY:
0.0000399
AC XY:
29
AN XY:
727230
show subpopulations
Gnomad4 AFR exome
AF:
0.000627
Gnomad4 AMR exome
AF:
0.000112
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000252
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.000250
AC:
38
AN:
152198
Hom.:
0
Cov.:
32
AF XY:
0.000202
AC XY:
15
AN XY:
74412
show subpopulations
Gnomad4 AFR
AF:
0.000747
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000943
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000251
Hom.:
0
Bravo
AF:
0.000348
ESP6500AA
AF:
0.000681
AC:
3
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000906
AC:
11
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Dec 17, 2024
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.30
T
BayesDel_noAF
Benign
-0.29
CADD
Benign
0.10
DANN
Benign
0.85
Eigen
Benign
-1.7
Eigen_PC
Benign
-1.9
FATHMM_MKL
Benign
0.026
N
LIST_S2
Benign
0.34
T
M_CAP
Benign
0.024
T
MetaRNN
Benign
0.010
T
MetaSVM
Benign
-0.95
T
PROVEAN
Benign
-1.1
N
REVEL
Benign
0.12
Sift
Benign
0.38
T
Sift4G
Benign
0.21
T
Polyphen
0.0010
B
Vest4
0.057
MVP
0.040
ClinPred
0.0082
T
GERP RS
-11

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.

Other links and lift over

dbSNP: rs147225516; hg19: chr3-131068482; COSMIC: COSV101273256; API