Variant 1-26182555-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006314.3(CNKSR1):c.595C>T(p.Leu199Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,192 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CNKSR1
NM_006314.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.396

Variant links:

Genes affected

CNKSR1 (HGNC:19700): (connector enhancer of kinase suppressor of Ras 1) This gene encodes a protein containing several motifs involved in protein-protein interaction, including PDZ, PH (Pleckstrin homology), and SAM (sterile alpha motif) domains. The encoded protein acts as a scaffold component for receptor tyrosine kinase signaling and may mediate crosstalk between different signaling pathways. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

CNKSR1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CNKSR1	NM_006314.3 linkuse as main transcript	c.595C>T	p.Leu199Phe	missense_variant	6/21	ENST00000361530.11	NP_006305.2
CNKSR1	NM_001297647.2 linkuse as main transcript	c.595C>T	p.Leu199Phe	missense_variant	6/21		NP_001284576.1
CNKSR1	NM_001297648.2 linkuse as main transcript	c.-180C>T		5_prime_UTR_variant	6/21		NP_001284577.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNKSR1	ENST00000361530.11 linkuse as main transcript	c.595C>T	p.Leu199Phe	missense_variant	6/21	1	NM_006314.3	ENSP00000354609	P1	Q969H4-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461192

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726892

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 08, 2022

The c.595C>T (p.L199F) alteration is located in exon 6 (coding exon 6) of the CNKSR1 gene. This alteration results from a C to T substitution at nucleotide position 595, causing the leucine (L) at amino acid position 199 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.34

BayesDel_addAF

Benign

-0.044

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.41

.;T

Eigen

Benign

0.024

Eigen_PC

Benign

-0.17

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.76

T;T

M_CAP

Benign

0.024

MetaRNN

Uncertain

0.62

D;D

MetaSVM

Benign

-0.96

MutationAssessor

Pathogenic

3.3

M;M

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-3.4

D;D

REVEL

Benign

0.12

Sift

Pathogenic

0.0

D;D

Sift4G

Uncertain

0.0090

D;D

Polyphen

0.98

.;D

Vest4

0.57

MutPred

0.58

Gain of ubiquitination at K196 (P = 0.0707);Gain of ubiquitination at K196 (P = 0.0707);

MVP

0.32

MPC

0.71

ClinPred

0.99

GERP RS

1.4

Varity_R

0.47

gMVP

0.67

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over