1-26183819-AC-ACC

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

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

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNKSR1	NM_006314.3	c.851dupC	p.Gln285ThrfsTer29	frameshift_variant	Exon 9 of 21	ENST00000361530.11	NP_006305.2
CNKSR1	NM_001297647.2	c.872dupC	p.Gln292ThrfsTer29	frameshift_variant	Exon 9 of 21		NP_001284576.1
CNKSR1	NM_001297648.2	c.77dupC	p.Gln27ThrfsTer29	frameshift_variant	Exon 9 of 21		NP_001284577.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNKSR1	ENST00000361530.11	c.851dupC	p.Gln285ThrfsTer29	frameshift_variant	Exon 9 of 21	1	NM_006314.3	ENSP00000354609.6

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

GnomAD3 exomes AF: 0.000210 AC: 52 AN: 247884 Hom.: 0 AF XY: 0.000149 AC XY: 20 AN XY: 134606

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 SAS exome AF: 0.0000327

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

Gnomad4 AFR exome AF: 0.000305

Gnomad4 AMR exome AF: 0.0000780

Gnomad4 ASJ exome AF: 0.0000548

Gnomad4 EAS exome AF: 0.00216

Gnomad4 SAS exome AF: 0.0000120

Gnomad4 FIN exome AF: 0.000186

Gnomad4 NFE exome AF: 0.0000520

Gnomad4 OTH exome AF: 0.0000657

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

Gnomad4 AFR AF: 0.000156

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00115

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000348

Gnomad4 OTH AF: 0.000605

EpiCase AF: 0.0000546

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs781114848; hg19: chr1-26510310;