Variant 17-27597293-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001394583.1(KSR1):c.1325T>C(p.Leu442Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0000718 in 1,600,956 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000070 ( 0 hom. )

Consequence

KSR1
NM_001394583.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.11

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.24818471).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KSR1	NM_001394583.1 linkuse as main transcript	c.1325T>C	p.Leu442Pro	missense_variant	10/21	ENST00000644974.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KSR1	ENST00000644974.2 linkuse as main transcript	c.1325T>C	p.Leu442Pro	missense_variant	10/21		NM_001394583.1	P1

Frequencies

GnomAD3 genomes

AF:

0.0000855

AC:

AN:

152050

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000132

AC:

AN:

226524

Hom.:

AF XY:

0.000122

AC XY:

AN XY:

122482

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000439

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000495

Gnomad NFE exome

AF:

0.0000983

Gnomad OTH exome

AF:

0.000891

GnomAD4 exome

AF:

0.0000704

AC:

102

AN:

1448906

Hom.:

Cov.:

AF XY:

0.0000751

AC XY:

AN XY:

719444

show subpopulations

Gnomad4 AFR exome

AF:

0.0000302

Gnomad4 AMR exome

AF:

0.000376

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000114

Gnomad4 NFE exome

AF:

0.0000642

Gnomad4 OTH exome

AF:

0.000117

GnomAD4 genome

AF:

0.0000855

AC:

AN:

152050

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74248

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.000197

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000749

Hom.:

Bravo

AF:

0.000110

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000118

AC:

ExAC

AF:

0.0000991

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 09, 2021

The c.914T>C (p.L305P) alteration is located in exon 11 (coding exon 8) of the KSR1 gene. This alteration results from a T to C substitution at nucleotide position 914, causing the leucine (L) at amino acid position 305 to be replaced by a proline (P). 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

Uncertain

0.13

BayesDel_noAF

Pathogenic

0.29

Cadd

Pathogenic

Dann

Pathogenic

1.0

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.83

T;T;T;.;T;T

M_CAP

Uncertain

0.16

MetaRNN

Benign

0.25

T;T;T;T;T;T

MetaSVM

Uncertain

-0.12

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.77

Vest4

0.56

MVP

0.95

MPC

1.5

ClinPred

0.23

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

gMVP

0.44

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