chr3-49804670-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_203370.2(INKA1):​c.541C>T​(p.Arg181Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000089 in 1,460,844 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

INKA1
NM_203370.2 missense

Scores

12
4
1

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.24
Variant links:
Genes affected
INKA1 (HGNC:32480): (inka box actin regulator 1) Enables protein kinase binding activity and protein serine/threonine kinase inhibitor activity. Predicted to be involved in negative regulation of catalytic activity. Predicted to act upstream of or within neural tube development. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.937

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
INKA1NM_203370.2 linkc.541C>T p.Arg181Cys missense_variant Exon 2 of 2 ENST00000333323.6 NP_976248.2
INKA1NM_001366281.1 linkc.460C>T p.Arg154Cys missense_variant Exon 2 of 2 NP_001353210.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
INKA1ENST00000333323.6 linkc.541C>T p.Arg181Cys missense_variant Exon 2 of 2 1 NM_203370.2 ENSP00000329735.5 A0A499FIG1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000890
AC:
13
AN:
1460844
Hom.:
0
Cov.:
32
AF XY:
0.0000110
AC XY:
8
AN XY:
726750
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:
0.0000464
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000809
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Sep 30, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.547C>T (p.R183C) alteration is located in exon 2 (coding exon 2) of the FAM212A gene. This alteration results from a C to T substitution at nucleotide position 547, causing the arginine (R) at amino acid position 183 to be replaced by a cysteine (C). 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
Pathogenic
0.74
BayesDel_addAF
Pathogenic
0.42
D
BayesDel_noAF
Pathogenic
0.36
CADD
Pathogenic
27
DANN
Pathogenic
1.0
Eigen
Pathogenic
0.73
Eigen_PC
Pathogenic
0.70
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Pathogenic
0.99
D
M_CAP
Uncertain
0.12
D
MetaRNN
Pathogenic
0.94
D
MetaSVM
Uncertain
-0.063
T
PrimateAI
Uncertain
0.74
T
PROVEAN
Pathogenic
-8.0
D
REVEL
Pathogenic
0.76
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Vest4
0.95
MVP
0.18
MPC
1.5
ClinPred
1.0
D
GERP RS
5.4

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: rs2081415833; hg19: chr3-49842103; COSMIC: COSV104412487; COSMIC: COSV104412487; API