Variant 2-29152745-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024692.6(CLIP4):c.1082A>G(p.His361Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000103 in 1,461,478 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

CLIP4
NM_024692.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.43

Variant links:

Genes affected

CLIP4 (HGNC:26108): (CAP-Gly domain containing linker protein family member 4) Predicted to enable microtubule plus-end binding activity. Predicted to be involved in cytoplasmic microtubule organization. Located in intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

CLIP4 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.117222905).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLIP4	NM_024692.6 linkuse as main transcript	c.1082A>G	p.His361Arg	missense_variant	9/16	ENST00000320081.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLIP4	ENST00000320081.10 linkuse as main transcript	c.1082A>G	p.His361Arg	missense_variant	9/16	1	NM_024692.6	P1	Q8N3C7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000797

AC:

AN:

250908

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135592

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000103

AC:

AN:

1461478

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

727016

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:

0.000174

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

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

Feb 23, 2023

The c.1082A>G (p.H361R) alteration is located in exon 9 (coding exon 8) of the CLIP4 gene. This alteration results from a A to G substitution at nucleotide position 1082, causing the histidine (H) at amino acid position 361 to be replaced by an arginine (R). 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

0.067

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.50

Cadd

Benign

8.1

Dann

Benign

0.53

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.56

FATHMM_MKL

Benign

0.086

LIST_S2

Benign

0.70

T;T;.;T

M_CAP

Benign

0.018

MetaRNN

Benign

0.12

T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.33

N;.;N;N

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.35

PROVEAN

Benign

0.0

N;N;N;N

REVEL

Benign

0.15

Sift

Benign

0.73

T;T;T;T

Sift4G

Benign

0.62

T;T;T;T

Polyphen

0.0040

.;.;B;B

Vest4

0.13

MutPred

0.33

Gain of MoRF binding (P = 0.0212);.;Gain of MoRF binding (P = 0.0212);Gain of MoRF binding (P = 0.0212);

MVP

0.75

MPC

0.13

ClinPred

0.055

GERP RS

4.9

Varity_R

0.033

gMVP

0.26

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