Variant 16-2179641-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_020764.4(CASKIN1):c.3727C>T(p.Pro1243Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000756 in 1,489,294 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00050 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00079 ( 1 hom. )

Consequence

CASKIN1
NM_020764.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.89

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.026690722).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASKIN1	NM_020764.4 linkuse as main transcript	c.3727C>T	p.Pro1243Ser	missense_variant	18/20	ENST00000343516.8	NP_065815.1
CASKIN1	XM_024450361.2 linkuse as main transcript	c.3514C>T	p.Pro1172Ser	missense_variant	16/18		XP_024306129.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASKIN1	ENST00000343516.8 linkuse as main transcript	c.3727C>T	p.Pro1243Ser	missense_variant	18/20	1	NM_020764.4	ENSP00000345436	P1

Frequencies

GnomAD3 genomes

AF:

0.000500

AC:

AN:

152038

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

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:

0.000824

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000464

AC:

AN:

99114

Hom.:

AF XY:

0.000511

AC XY:

AN XY:

52874

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000525

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000101

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000850

Gnomad OTH exome

AF:

0.000381

GnomAD4 exome

AF:

0.000785

AC:

1050

AN:

1337138

Hom.:

Cov.:

AF XY:

0.000738

AC XY:

484

AN XY:

655600

show subpopulations

Gnomad4 AFR exome

AF:

0.000207

Gnomad4 AMR exome

AF:

0.000926

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000243

Gnomad4 NFE exome

AF:

0.000930

Gnomad4 OTH exome

AF:

0.000652

GnomAD4 genome

AF:

0.000499

AC:

AN:

152156

Hom.:

Cov.:

AF XY:

0.000484

AC XY:

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.000457

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000824

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000378

Hom.:

Bravo

AF:

0.000563

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000624

AC:

ExAC

AF:

0.000340

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

Aug 30, 2022

The c.3727C>T (p.P1243S) alteration is located in exon 18 (coding exon 18) of the CASKIN1 gene. This alteration results from a C to T substitution at nucleotide position 3727, causing the proline (P) at amino acid position 1243 to be replaced by a serine (S). 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

0.075

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.020

Eigen

Uncertain

0.30

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.73

M_CAP

Uncertain

0.17

MetaRNN

Benign

0.027

MetaSVM

Benign

-0.80

MutationAssessor

Benign

2.0

MutationTaster

Benign

0.62

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-2.3

REVEL

Benign

0.086

Sift

Benign

0.11

Sift4G

Benign

0.11

Polyphen

1.0

Vest4

0.32

MVP

0.63

MPC

0.97

ClinPred

0.039

GERP RS

3.5

Varity_R

0.11

gMVP

0.14

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