dbSNP rs2275336: CNKSR3:n.1956C>T (chr6-154405854-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000433165.6(CNKSR3):n.1956C>T variant causes a non coding transcript exon 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
ENST00000433165.6 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.897

Publications

13 publications found

Variant links:

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]

CNKSR3 links:

ENSG00000288520 (HGNC:):

ENSG00000288520 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CNKSR3	NM_173515.4 link	c.*500C>T		3_prime_UTR_variant	Exon 13 of 13	ENST00000607772.6	NP_775786.2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CNKSR3	ENST00000433165.6 link	n.1956C>T	non_coding_transcript_exon_variant	Exon 10 of 10	1
CNKSR3	ENST00000607772.6 link	c.*500C>T	3_prime_UTR_variant	Exon 13 of 13	1	NM_173515.4	ENSP00000475915.1	Q6P9H4-1
ENSG00000288520	ENST00000673182.1 link	c.1369+4489C>T	intron_variant	Intron 12 of 21			ENSP00000499846.1

Frequencies

GnomAD3 genomes

AF:

0.0634

AC:

9633

AN:

151920

Hom.:

530

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.0683

AC XY:

202

AN XY:

2958

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.203

AC:

257

AN:

1266

Ashkenazi Jewish (ASJ)

AF:

0.0455

AC:

AN:

East Asian (EAS)

AF:

0.00538

AC:

AN:

186

South Asian (SAS)

AF:

0.0553

AC:

AN:

470

European-Finnish (FIN)

AF:

0.0319

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0323

AC:

117

AN:

3618

Other (OTH)

AF:

0.0234

AC:

AN:

256

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0635

AC:

9657

AN:

152038

Hom.:

541

Cov.:

AF XY:

0.0654

AC XY:

4862

AN XY:

74286

show subpopulations

African (AFR)

AF:

0.0631

AC:

2617

AN:

41496

American (AMR)

AF:

0.197

AC:

3006

AN:

15248

Ashkenazi Jewish (ASJ)

AF:

0.0334

AC:

116

AN:

3468

East Asian (EAS)

AF:

0.0171

AC:

AN:

5142

South Asian (SAS)

AF:

0.0587

AC:

282

AN:

4808

European-Finnish (FIN)

AF:

0.0403

AC:

427

AN:

10590

Middle Eastern (MID)

AF:

0.0578

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0429

AC:

2917

AN:

67970

Other (OTH)

AF:

0.0640

AC:

135

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

433

867

1300

1734

2167

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

106

212

318

424

530

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0514

Hom.:

1352

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

(source)

DANN

Benign

0.51

PhyloP100

0.90

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over