16-2179835-C-T

Variant summary

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

The NM_020764.4(CASKIN1):​c.3533G>A​(p.Arg1178His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000691 in 1,447,320 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

CASKIN1
NM_020764.4 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.46
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]

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=0.118263215).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CASKIN1NM_020764.4 linkuse as main transcriptc.3533G>A p.Arg1178His missense_variant 18/20 ENST00000343516.8 NP_065815.1
CASKIN1XM_024450361.2 linkuse as main transcriptc.3320G>A p.Arg1107His missense_variant 16/18 XP_024306129.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CASKIN1ENST00000343516.8 linkuse as main transcriptc.3533G>A p.Arg1178His missense_variant 18/201 NM_020764.4 ENSP00000345436 P1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.91e-7
AC:
1
AN:
1447320
Hom.:
0
Cov.:
37
AF XY:
0.00
AC XY:
0
AN XY:
719090
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

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 submitterclinical testingAmbry GeneticsDec 21, 2022The c.3533G>A (p.R1178H) alteration is located in exon 18 (coding exon 18) of the CASKIN1 gene. This alteration results from a G to A substitution at nucleotide position 3533, causing the arginine (R) at amino acid position 1178 to be replaced by a histidine (H). 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
0.088
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.47
CADD
Benign
19
DANN
Benign
0.96
DEOGEN2
Benign
0.019
T
Eigen
Benign
-0.62
Eigen_PC
Benign
-0.60
FATHMM_MKL
Benign
0.11
N
LIST_S2
Benign
0.82
T
M_CAP
Uncertain
0.18
D
MetaRNN
Benign
0.12
T
MetaSVM
Benign
-0.92
T
MutationAssessor
Benign
0.40
N
MutationTaster
Benign
0.96
N
PrimateAI
Uncertain
0.78
T
PROVEAN
Benign
-1.4
N
REVEL
Benign
0.027
Sift
Benign
0.13
T
Sift4G
Benign
0.070
T
Polyphen
0.014
B
Vest4
0.17
MutPred
0.40
Loss of MoRF binding (P = 0.0318);
MVP
0.51
MPC
0.35
ClinPred
0.17
T
GERP RS
1.5
Varity_R
0.074
gMVP
0.12

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.

Other links and lift over

hg19: chr16-2229836; COSMIC: COSV58218847; COSMIC: COSV58218847; API