Variant 1-112456324-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_018704.3(CTTNBP2NL):c.832G>A(p.Glu278Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000589 in 1,613,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000060 ( 0 hom. )

Consequence

CTTNBP2NL
NM_018704.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.67

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.056992173).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTTNBP2NL	NM_018704.3 linkuse as main transcript	c.832G>A	p.Glu278Lys	missense_variant	6/6	ENST00000271277.11	NP_061174.1	Q9P2B4
CTTNBP2NL	XM_011541781.3 linkuse as main transcript	c.832G>A	p.Glu278Lys	missense_variant	6/6		XP_011540083.1	Q9P2B4
CTTNBP2NL	XM_017001806.2 linkuse as main transcript	c.832G>A	p.Glu278Lys	missense_variant	6/6		XP_016857295.1	Q9P2B4
CTTNBP2NL	XM_047425362.1 linkuse as main transcript	c.832G>A	p.Glu278Lys	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.832G>A	p.Glu278Lys	missense_variant	6/6	1	NM_018704.3	ENSP00000271277.6		Q9P2B4
CTTNBP2NL	ENST00000441739.1 linkuse as main transcript	c.*18G>A		downstream_gene_variant		3		ENSP00000390976.1		B1AMN7

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000148

AC:

AN:

249712

Hom.:

AF XY:

0.000126

AC XY:

AN XY:

135318

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000898

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000178

Gnomad OTH exome

AF:

0.000659

GnomAD4 exome

AF:

0.0000595

AC:

AN:

1461740

Hom.:

Cov.:

AF XY:

0.0000605

AC XY:

AN XY:

727158

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000939

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:

0.0000360

Gnomad4 OTH exome

AF:

0.0000662

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152154

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000458

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.000106

ExAC

AF:

0.000140

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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

Nov 14, 2024

The c.832G>A (p.E278K) alteration is located in exon 6 (coding exon 4) of the CTTNBP2NL gene. This alteration results from a G to A substitution at nucleotide position 832, causing the glutamic acid (E) at amino acid position 278 to be replaced by a lysine (K). 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

0.11

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Benign

0.81

DEOGEN2

Benign

0.018

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.071

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.85

M_CAP

Benign

0.0072

MetaRNN

Benign

0.057

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

PrimateAI

Benign

0.41

PROVEAN

Benign

0.96

REVEL

Benign

0.17

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.18

Vest4

0.40

MutPred

0.56

Gain of MoRF binding (P = 0.0019);

MVP

0.66

MPC

0.23

ClinPred

0.056

GERP RS

6.1

Varity_R

0.072

gMVP

0.33

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