rs2275336

Positions:

• chr6-154405854-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173515.4(CNKSR3):​c.*500C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0637 in 158,004 control chromosomes in the GnomAD database, including 576 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.064 (541 hom., cov: 32)
  • Exomes 𝑓: 0.069 (35 hom.)
• Consequence: CNKSR3 NM_173515.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.897

Genes affected

CNKSR3 (HGNC:23034): (CNKSR family member 3) Predicted to be involved in negative regulation of ERK1 and ERK2 cascade; negative regulation of peptidyl-serine phosphorylation; and positive regulation of sodium ion transport. Predicted to act upstream of or within positive regulation of sodium ion transmembrane transporter activity. Predicted to be located in apical plasma membrane and cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNKSR3	NM_173515.4	c.*500C>T		3_prime_UTR_variant	13/13	ENST00000607772.6	NP_775786.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNKSR3	ENST00000607772.6	c.*500C>T		3_prime_UTR_variant	13/13	1	NM_173515.4	ENSP00000475915	P1
CNKSR3	ENST00000433165.6	n.1956C>T		non_coding_transcript_exon_variant	10/10	1

Frequencies

GnomAD3 genomes AF: 0.0634 AC: 9633 AN: 151920 Hom.: 530 Cov.: 32

Gnomad AFR AF: 0.0632

Gnomad AMI AF: 0.0570

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.0334

Gnomad EAS AF: 0.0171

Gnomad SAS AF: 0.0584

Gnomad FIN AF: 0.0403

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0429

Gnomad OTH AF: 0.0651

GnomAD4 exome AF: 0.0691 AC: 412 AN: 5966 Hom.: 35 Cov.: 0 AF XY: 0.0683 AC XY: 202 AN XY: 2958

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.203

Gnomad4 ASJ exome AF: 0.0455

Gnomad4 EAS exome AF: 0.00538

Gnomad4 SAS exome AF: 0.0553

Gnomad4 FIN exome AF: 0.0319

Gnomad4 NFE exome AF: 0.0323

Gnomad4 OTH exome AF: 0.0234

GnomAD4 genome AF: 0.0635 AC: 9657 AN: 152038 Hom.: 541 Cov.: 32 AF XY: 0.0654 AC XY: 4862 AN XY: 74286

Gnomad4 AFR AF: 0.0631

Gnomad4 AMR AF: 0.197

Gnomad4 ASJ AF: 0.0334

Gnomad4 EAS AF: 0.0171

Gnomad4 SAS AF: 0.0587

Gnomad4 FIN AF: 0.0403

Gnomad4 NFE AF: 0.0429

Gnomad4 OTH AF: 0.0640

Alfa AF: 0.0498 Hom.: 597

Bravo AF: 0.0752

Asia WGS AF: 0.0450 AC: 159 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.3
DANN	Benign	0.51

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: rs2275336; hg19: chr6-154726988;