6-154490463-A-G

Position:

• chr6-154490463-A-G

Variant summary

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

The NM_173515.4(CNKSR3):​c.52+19600T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.67 in 152,164 control chromosomes in the GnomAD database, including 34,695 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 0.67 (34695 hom., cov: 34)
• Consequence: CNKSR3 NM_173515.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50

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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.758 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNKSR3	NM_173515.4	c.52+19600T>C		intron_variant		ENST00000607772.6	NP_775786.2
CNKSR3	NM_001368116.1	c.70+19406T>C		intron_variant			NP_001355045.1
CNKSR3	NM_001368117.1	c.52+19600T>C		intron_variant			NP_001355046.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNKSR3	ENST00000607772.6	c.52+19600T>C		intron_variant		1	NM_173515.4	ENSP00000475915	P1

Frequencies

GnomAD3 genomes AF: 0.670 AC: 101892 AN: 152050 Hom.: 34647 Cov.: 34

Gnomad AFR AF: 0.764

Gnomad AMI AF: 0.481

Gnomad AMR AF: 0.650

Gnomad ASJ AF: 0.763

Gnomad EAS AF: 0.462

Gnomad SAS AF: 0.536

Gnomad FIN AF: 0.566

Gnomad MID AF: 0.761

Gnomad NFE AF: 0.655

Gnomad OTH AF: 0.705

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.670 AC: 101999 AN: 152164 Hom.: 34695 Cov.: 34 AF XY: 0.662 AC XY: 49251 AN XY: 74374

Gnomad4 AFR AF: 0.765

Gnomad4 AMR AF: 0.650

Gnomad4 ASJ AF: 0.763

Gnomad4 EAS AF: 0.462

Gnomad4 SAS AF: 0.537

Gnomad4 FIN AF: 0.566

Gnomad4 NFE AF: 0.655

Gnomad4 OTH AF: 0.702

Alfa AF: 0.662 Hom.: 5379

Bravo AF: 0.683

Asia WGS AF: 0.575 AC: 1996 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.094
DANN	Benign	0.36

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: rs1572662; hg19: chr6-154811597;