3-49804919-C-T

Variant names:

• chr3-49804919-C-T
• rs745844777
• NM_203370.2:c.790C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_203370.2(INKA1):​c.790C>T​(p.Arg264Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,460,676 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: INKA1 NM_203370.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.62
• Publications: 2 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_203370.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INKA1	NM_203370.2	MANE Select	c.790C>T	p.Arg264Cys	missense	Exon 2 of 2	NP_976248.2	A0A499FIG1
	INKA1	NM_001366281.1		c.709C>T	p.Arg237Cys	missense	Exon 2 of 2	NP_001353210.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INKA1	ENST00000333323.6	TSL:1 MANE Select	c.790C>T	p.Arg264Cys	missense	Exon 2 of 2	ENSP00000329735.5	A0A499FIG1
	INKA1	ENST00000893014.1		c.742C>T	p.Arg248Cys	missense	Exon 2 of 2	ENSP00000563073.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000121 AC: 3 AN: 248084 AF XY: 0.00000744

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000181

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000103 AC: 15 AN: 1460676 Hom.: 0 Cov.: 32 AF XY: 0.00000963 AC XY: 7 AN XY: 726620

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52292

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5756

European-Non Finnish (NFE) AF: 0.0000117 AC: 13 AN: 1111960

Other (OTH) AF: 0.00 AC: 0 AN: 60380

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000247 AC: 3

EpiCase AF: 0.000109

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.025	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	24
DANN	Uncertain	1.0
Eigen	Uncertain	0.22
Eigen_PC	Benign	0.17
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.64	D
MetaSVM	Benign	-0.59	T
PhyloP100		1.6
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.16
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.010	D
Vest4		0.69
MVP		0.081
MPC		1.4
ClinPred		0.81	D
GERP RS		5.7
Mutation Taster		=73/27	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs745844777; hg19: chr3-49842352; COSMIC: COSV60968685; COSMIC: COSV60968685;