9-124302004-T-C

Position:

• chr9-124302004-T-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The ENST00000320246.10(NEK6):​c.40T>C​(p.Ser14Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: NEK6 ENST00000320246.10 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.49

Genes affected

NEK6 (HGNC:7749): (NIMA related kinase 6) The protein encoded by this gene is a kinase required for progression through the metaphase portion of mitosis. Inhibition of the encoded protein can lead to apoptosis. This protein also can enhance tumorigenesis by suppressing tumor cell senescence. Several transcript variants encoding a few different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

ACMG classification

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=0.04835853).
• BP6: Variant 9-124302004-T-C is Benign according to our data. Variant chr9-124302004-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2256385.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEK6	NM_014397.6	c.40T>C	p.Ser14Pro	missense_variant	2/10	ENST00000320246.10	NP_055212.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NEK6	ENST00000320246.10	c.40T>C	p.Ser14Pro	missense_variant	2/10	1	NM_014397.6	ENSP00000319734	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 22, 2021

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
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.035	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	15
DANN	Benign	0.45
DEOGEN2	Benign	0.0072	.;T;.;T;T;T;T;T;.;.;T;T;.;.;T
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.073	N
LIST_S2	Benign	0.57	T;.;.;.;.;T;T;T;T;T;T;T;T;T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.048	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.69	.;N;.;N;N;.;.;.;.;.;N;.;.;.;.
MutationTaster	Benign	1.0	N;N;N;N;N;N;N;N
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	0.27	N;N;N;N;N;N;N;N;N;N;N;N;N;N;N
REVEL	Benign	0.14
Sift	Benign	0.38	T;T;T;T;T;T;D;T;T;T;T;T;T;T;T
Sift4G	Benign	0.31	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
Polyphen		0.0	B;B;B;B;B;.;.;.;.;.;B;.;B;B;.
Vest4		0.19
MutPred		0.14		.;Gain of glycosylation at S13 (P = 0.1031);.;Gain of glycosylation at S13 (P = 0.1031);Gain of glycosylation at S13 (P = 0.1031);Gain of glycosylation at S13 (P = 0.1031);Gain of glycosylation at S13 (P = 0.1031);Gain of glycosylation at S13 (P = 0.1031);Gain of glycosylation at S13 (P = 0.1031);.;Gain of glycosylation at S13 (P = 0.1031);Gain of glycosylation at S13 (P = 0.1031);.;.;Gain of glycosylation at S13 (P = 0.1031);
MVP		0.43
MPC		0.42
ClinPred		0.058	T
GERP RS		3.0
Varity_R		0.059
gMVP		0.15

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-127064283;