Variant 16-2178641-G-A 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_020764.4(CASKIN1):c.4205C>T(p.Ser1402Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000012 in 1,589,390 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

CASKIN1
NM_020764.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.349

Variant links:

Genes affected

CASKIN1 (HGNC:20879): (CASK interacting protein 1) Enables identical protein binding activity. Predicted to be involved in signal transduction. Predicted to be active in cytoplasm and membrane. [provided by Alliance of Genome Resources, Apr 2022]

CASKIN1 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=0.18959248).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASKIN1	NM_020764.4 linkuse as main transcript	c.4205C>T	p.Ser1402Leu	missense_variant	20/20	ENST00000343516.8	NP_065815.1
CASKIN1	XM_024450361.2 linkuse as main transcript	c.3992C>T	p.Ser1331Leu	missense_variant	18/18		XP_024306129.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASKIN1	ENST00000343516.8 linkuse as main transcript	c.4205C>T	p.Ser1402Leu	missense_variant	20/20	1	NM_020764.4	ENSP00000345436	P1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000230

AC:

AN:

217204

Hom.:

AF XY:

0.0000165

AC XY:

AN XY:

120964

show subpopulations

Gnomad AFR exome

AF:

0.0000855

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000104

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000101

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000111

AC:

AN:

1437272

Hom.:

Cov.:

AF XY:

0.0000154

AC XY:

AN XY:

715576

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:

0.000165

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.04e-7

Gnomad4 OTH exome

AF:

0.0000168

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152118

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000302

ExAC

AF:

0.00000835

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 22, 2022

The c.4205C>T (p.S1402L) alteration is located in exon 20 (coding exon 20) of the CASKIN1 gene. This alteration results from a C to T substitution at nucleotide position 4205, causing the serine (S) at amino acid position 1402 to be replaced by a leucine (L). 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

Benign

0.098

BayesDel_addAF

Benign

-0.098

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.017

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.54

FATHMM_MKL

Benign

0.38

LIST_S2

Benign

0.59

M_CAP

Pathogenic

0.34

MetaRNN

Benign

0.19

MetaSVM

Benign

-0.91

MutationAssessor

Uncertain

2.3

MutationTaster

Benign

0.97

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-2.2

REVEL

Benign

0.099

Sift

Uncertain

0.0080

Sift4G

Benign

0.080

Polyphen

0.80

Vest4

0.067

MutPred

0.18

Loss of phosphorylation at S1402 (P = 0.0068);

MVP

0.57

MPC

0.25

ClinPred

0.058

GERP RS

3.4

Varity_R

0.075

gMVP

0.11

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.

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