chr17-4988838-C-T

Variant summary

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

The NM_001394789.1(INCA1):​c.502G>A​(p.Glu168Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,614,132 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

INCA1
NM_001394789.1 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.733
Variant links:
Genes affected
INCA1 (HGNC:32224): (inhibitor of CDK, cyclin A1 interacting protein 1) Enables cyclin binding activity; cyclin-dependent protein serine/threonine kinase inhibitor activity; and identical protein binding activity. Acts upstream of or within negative regulation of cyclin-dependent protein serine/threonine kinase activity. Located in cytoplasm and nuclear body. [provided by Alliance of Genome Resources, Apr 2022]
CAMTA2-AS1 (HGNC:55342): (CAMTA2 antisense RNA 1)

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=0.06824747).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
INCA1NM_001394789.1 linkc.502G>A p.Glu168Lys missense_variant Exon 6 of 7 ENST00000695324.1 NP_001381718.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
INCA1ENST00000695324.1 linkc.502G>A p.Glu168Lys missense_variant Exon 6 of 7 NM_001394789.1 ENSP00000511805.1 Q0VD86-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152244
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.00000398
AC:
1
AN:
251226
Hom.:
0
AF XY:
0.00000737
AC XY:
1
AN XY:
135776
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000881
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000410
AC:
6
AN:
1461888
Hom.:
0
Cov.:
32
AF XY:
0.00000550
AC XY:
4
AN XY:
727244
show subpopulations
Gnomad4 AFR exome
AF:
0.0000597
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152244
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74378
show subpopulations
Gnomad4 AFR
AF:
0.00
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
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 20, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.502G>A (p.E168K) alteration is located in exon 8 (coding exon 5) of the INCA1 gene. This alteration results from a G to A substitution at nucleotide position 502, causing the glutamic acid (E) at amino acid position 168 to be replaced by a lysine (K). 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
0.092
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.42
CADD
Benign
19
DANN
Uncertain
1.0
DEOGEN2
Benign
0.40
.;.;T;T
Eigen
Benign
-0.69
Eigen_PC
Benign
-0.70
FATHMM_MKL
Benign
0.067
N
LIST_S2
Benign
0.69
.;T;.;T
M_CAP
Benign
0.0029
T
MetaRNN
Benign
0.068
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.55
.;.;N;N
PrimateAI
Benign
0.30
T
PROVEAN
Uncertain
-2.8
D;.;.;.
REVEL
Benign
0.036
Sift
Benign
0.073
T;.;.;.
Sift4G
Uncertain
0.024
D;D;D;D
Polyphen
0.019
B;B;B;B
Vest4
0.18
MutPred
0.42
.;.;Gain of ubiquitination at E168 (P = 0.0045);Gain of ubiquitination at E168 (P = 0.0045);
MVP
0.18
ClinPred
0.10
T
GERP RS
2.4
Varity_R
0.17
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.

Other links and lift over

dbSNP: rs762262485; hg19: chr17-4892133; API