1-26183819-ACC-ACCC

Variant names:

• chr1-26183819-A-AC
• rs781114848
• NM_006314.3:c.851dupC

Variant summary

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

The NM_006314.3(CNKSR1):​c.851dupC​(p.Gln285ThrfsTer29) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000965 in 1,336,204 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.000099 (0 hom., cov: 28)
  • Exomes 𝑓: 0.000096 (0 hom.)
• Consequence: CNKSR1 NM_006314.3 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.256
• Publications: 1 publications found

Genes affected

CNKSR1 (HGNC:19700): (connector enhancer of kinase suppressor of Ras 1) This gene encodes a protein containing several motifs involved in protein-protein interaction, including PDZ, PH (Pleckstrin homology), and SAM (sterile alpha motif) domains. The encoded protein acts as a scaffold component for receptor tyrosine kinase signaling and may mediate crosstalk between different signaling pathways. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

CNKSR1 Gene-Disease associations (from GenCC):

• intellectual disability

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics
• neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: G2P

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006314.3. 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
	CNKSR1	NM_006314.3	MANE Select	c.851dupC	p.Gln285ThrfsTer29	frameshift	Exon 9 of 21	NP_006305.2	Q53GM7
	CNKSR1	NM_001297647.2		c.872dupC	p.Gln292ThrfsTer29	frameshift	Exon 9 of 21	NP_001284576.1	Q969H4-1
	CNKSR1	NM_001297648.2		c.77dupC	p.Gln27ThrfsTer29	frameshift	Exon 9 of 21	NP_001284577.1	G3V160

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNKSR1	ENST00000361530.11	TSL:1 MANE Select	c.851dupC	p.Gln285ThrfsTer29	frameshift	Exon 9 of 21	ENSP00000354609.6	Q969H4-2
	CNKSR1	ENST00000374253.9	TSL:1	c.872dupC	p.Gln292ThrfsTer29	frameshift	Exon 9 of 21	ENSP00000363371.5	Q969H4-1
	CNKSR1	ENST00000878394.1		c.872dupC	p.Gln292ThrfsTer41	frameshift	Exon 9 of 21	ENSP00000548453.1

Frequencies

GnomAD3 genomes AF: 0.0000995 AC: 12 AN: 120584 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.000156

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00114

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000348

Gnomad OTH AF: 0.000609

GnomAD2 exomes AF: 0.000210 AC: 52 AN: 247884 AF XY: 0.000149

Gnomad AFR exome AF: 0.000434

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.000300

Gnomad EAS exome AF: 0.00164

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000812

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.0000963 AC: 117 AN: 1215564 Hom.: 0 Cov.: 29 AF XY: 0.0000824 AC XY: 50 AN XY: 606716

African (AFR) AF: 0.000305 AC: 8 AN: 26220

American (AMR) AF: 0.0000780 AC: 3 AN: 38450

Ashkenazi Jewish (ASJ) AF: 0.0000548 AC: 1 AN: 18234

East Asian (EAS) AF: 0.00216 AC: 44 AN: 20372

South Asian (SAS) AF: 0.0000120 AC: 1 AN: 83000

European-Finnish (FIN) AF: 0.000186 AC: 7 AN: 37546

Middle Eastern (MID) AF: 0.000217 AC: 1 AN: 4602

European-Non Finnish (NFE) AF: 0.0000520 AC: 49 AN: 941468

Other (OTH) AF: 0.0000657 AC: 3 AN: 45672

GnomAD4 genome AF: 0.0000995 AC: 12 AN: 120640 Hom.: 0 Cov.: 28 AF XY: 0.000104 AC XY: 6 AN XY: 57782

African (AFR) AF: 0.000156 AC: 5 AN: 32072

American (AMR) AF: 0.00 AC: 0 AN: 11876

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3002

East Asian (EAS) AF: 0.00115 AC: 4 AN: 3488

South Asian (SAS) AF: 0.00 AC: 0 AN: 2910

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7066

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 242

European-Non Finnish (NFE) AF: 0.0000348 AC: 2 AN: 57528

Other (OTH) AF: 0.000605 AC: 1 AN: 1654

Alfa AF: 0.000111 Hom.: 10

EpiCase AF: 0.0000546

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.26
Mutation Taster		=18/182	disease causing (fs/PTC)

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

Other links and lift over

dbSNP: rs781114848; hg19: chr1-26510310; COSMIC: COSV64163557; COSMIC: COSV64163557;