Variant 1-112455947-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_018704.3(CTTNBP2NL):c.455C>T(p.Ser152Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00004 in 1,576,860 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000040 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000040 ( 0 hom. )

Consequence

CTTNBP2NL
NM_018704.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.89

Variant links:

Genes affected

CTTNBP2NL (HGNC:25330): (CTTNBP2 N-terminal like) Enables protein phosphatase 2A binding activity. Acts upstream of or within negative regulation of transmembrane transport; negative regulation of transporter activity; and protein dephosphorylation. Located in actin cytoskeleton. [provided by Alliance of Genome Resources, Apr 2022]

CTTNBP2NL links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.39996523).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTTNBP2NL	NM_018704.3 linkuse as main transcript	c.455C>T	p.Ser152Phe	missense_variant	6/6	ENST00000271277.11	NP_061174.1	Q9P2B4
CTTNBP2NL	XM_011541781.3 linkuse as main transcript	c.455C>T	p.Ser152Phe	missense_variant	6/6		XP_011540083.1	Q9P2B4
CTTNBP2NL	XM_017001806.2 linkuse as main transcript	c.455C>T	p.Ser152Phe	missense_variant	6/6		XP_016857295.1	Q9P2B4
CTTNBP2NL	XM_047425362.1 linkuse as main transcript	c.455C>T	p.Ser152Phe	missense_variant	6/6		XP_047281318.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTTNBP2NL	ENST00000271277.11 linkuse as main transcript	c.455C>T	p.Ser152Phe	missense_variant	6/6	1	NM_018704.3	ENSP00000271277.6		Q9P2B4
CTTNBP2NL	ENST00000441739.1 linkuse as main transcript	c.455C>T	p.Ser152Phe	missense_variant	6/6	3		ENSP00000390976.1		B1AMN7

Frequencies

GnomAD3 genomes

AF:

0.0000395

AC:

AN:

151820

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000883

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000400

AC:

AN:

1425040

Hom.:

Cov.:

AF XY:

0.0000396

AC XY:

AN XY:

706604

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000519

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000395

AC:

AN:

151820

Hom.:

Cov.:

AF XY:

0.0000405

AC XY:

AN XY:

74134

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000883

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000564

Hom.:

Bravo

AF:

0.0000302

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 13, 2022

The c.455C>T (p.S152F) alteration is located in exon 6 (coding exon 4) of the CTTNBP2NL gene. This alteration results from a C to T substitution at nucleotide position 455, causing the serine (S) at amino acid position 152 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.32

BayesDel_addAF

Benign

-0.0052

BayesDel_noAF

Benign

-0.25

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

T;T

Eigen

Pathogenic

0.75

Eigen_PC

Pathogenic

0.77

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.85

D;T

M_CAP

Benign

0.027

MetaRNN

Benign

0.40

T;T

MetaSVM

Benign

-0.78

MutationAssessor

Benign

1.9

L;.

PrimateAI

Uncertain

0.78

PROVEAN

Uncertain

-2.7

D;D

REVEL

Benign

0.21

Sift

Benign

0.047

D;D

Sift4G

Benign

0.077

T;T

Polyphen

1.0

D;.

Vest4

0.37

MutPred

0.43

Loss of phosphorylation at S152 (P = 0.0233);Loss of phosphorylation at S152 (P = 0.0233);

MVP

0.68

MPC

0.44

ClinPred

0.88

GERP RS

6.1

Varity_R

0.13

gMVP

0.099

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over