Variant 17-27582997-C-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001394583.1(KSR1):c.872C>A(p.Pro291Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000122 in 1,609,130 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 27)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

KSR1
NM_001394583.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.57

Variant links:

Genes affected

KSR1 (HGNC:6465): (kinase suppressor of ras 1) Enables 14-3-3 protein binding activity; ATP binding activity; and protein C-terminus binding activity. Involved in positive regulation of MAPK cascade. Located in endoplasmic reticulum and membrane. Part of protein-containing complex. Implicated in breast adenocarcinoma. Biomarker of breast cancer. [provided by Alliance of Genome Resources, Apr 2022]

KSR1 links:

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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	UniProt
KSR1	NM_001394583.1 linkuse as main transcript	c.872C>A	p.Pro291Gln	missense_variant	4/21	ENST00000644974.2	NP_001381512.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KSR1	ENST00000644974.2 linkuse as main transcript	c.872C>A	p.Pro291Gln	missense_variant	4/21		NM_001394583.1	ENSP00000494552	P1

Frequencies

GnomAD3 genomes

AF:

0.000119

AC:

AN:

151746

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000727

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000263

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000801

AC:

AN:

237334

Hom.:

AF XY:

0.0000539

AC XY:

AN XY:

129864

show subpopulations

Gnomad AFR exome

AF:

0.000147

Gnomad AMR exome

AF:

0.000178

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000115

Gnomad SAS exome

AF:

0.0000338

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000657

Gnomad OTH exome

AF:

0.000172

GnomAD4 exome

AF:

0.000122

AC:

178

AN:

1457266

Hom.:

Cov.:

AF XY:

0.000112

AC XY:

AN XY:

724652

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.000180

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000304

Gnomad4 SAS exome

AF:

0.0000584

Gnomad4 FIN exome

AF:

0.0000382

Gnomad4 NFE exome

AF:

0.000129

Gnomad4 OTH exome

AF:

0.0000665

GnomAD4 genome

AF:

0.000119

AC:

AN:

151864

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

74216

show subpopulations

Gnomad4 AFR

AF:

0.0000725

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000195

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000907

ExAC

AF:

0.0000747

AC:

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

Nov 10, 2022

The c.461C>A (p.P154Q) alteration is located in exon 5 (coding exon 2) of the KSR1 gene. This alteration results from a C to A substitution at nucleotide position 461, causing the proline (P) at amino acid position 154 to be replaced by a glutamine (Q). 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

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.15

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.59

.;D;.;.;.;.;T

Eigen

Pathogenic

0.83

Eigen_PC

Pathogenic

0.78

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.97

D;T;D;D;.;D;D

M_CAP

Uncertain

0.10

MetaRNN

Uncertain

0.72

D;D;D;D;D;D;D

MetaSVM

Uncertain

-0.065

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.69

REVEL

Uncertain

0.51

Sift4G

Pathogenic

0.0

.;D;D;D;D;.;D

Vest4

0.61

MVP

0.69

MPC

1.1

ClinPred

0.88

GERP RS

5.7

gMVP

0.47

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