19-36018938-G-C

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_015526.3(CLIP3):c.1143C>G(p.Asp381Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,613,230 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

CLIP3
NM_015526.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.17

Variant links:

Genes affected

CLIP3 (HGNC:24314): (CAP-Gly domain containing linker protein 3) This gene encodes a member of the cytoplasmic linker protein 170 family. Members of this protein family contain a cytoskeleton-associated protein glycine-rich domain and mediate the interaction of microtubules with cellular organelles. The encoded protein plays a role in T cell apoptosis by facilitating the association of tubulin and the lipid raft ganglioside GD3. The encoded protein also functions as a scaffold protein mediating membrane localization of phosphorylated protein kinase B. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Dec 2010]

CLIP3 links:

ENSG00000267698 (HGNC:):

ENSG00000267698 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.13936517).

BS2

High AC in GnomAdExome4 at 20 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLIP3	NM_015526.3 link	c.1143C>G	p.Asp381Glu	missense_variant	Exon 9 of 14	ENST00000360535.9	NP_056341.1	Q96DZ5
CLIP3	NM_001199570.2 link	c.1143C>G	p.Asp381Glu	missense_variant	Exon 8 of 13		NP_001186499.1	Q96DZ5
LOC101927572	NR_170987.1 link	n.235-296G>C		intron_variant	Intron 2 of 3
LOC101927572	NR_170988.1 link	n.235-296G>C		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CLIP3	ENST00000360535.9 link	c.1143C>G	p.Asp381Glu	missense_variant	Exon 9 of 14	1	NM_015526.3	ENSP00000353732.3	Q96DZ5
ENSG00000267698	ENST00000586962.1 link	n.229-296G>C		intron_variant	Intron 2 of 3	1
CLIP3	ENST00000593074.5 link	c.1143C>G	p.Asp381Glu	missense_variant	Exon 8 of 13	2		ENSP00000466832.1	Q96DZ5
ENSG00000267698	ENST00000685157.1 link	n.244-296G>C		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152228

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:

0.000827

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000320

AC:

AN:

250150

Hom.:

AF XY:

0.0000370

AC XY:

AN XY:

135166

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000272

Gnomad SAS exome

AF:

0.0000985

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000137

AC:

AN:

1461002

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

726776

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.000151

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152228

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74366

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:

0.000827

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

AC:

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 03, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1143C>G (p.D381E) alteration is located in exon 8 (coding exon 8) of the CLIP3 gene. This alteration results from a C to G substitution at nucleotide position 1143, causing the aspartic acid (D) at amino acid position 381 to be replaced by a glutamic acid (E). 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

Pathogenic

0.61

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.21

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.074

T;T

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.19

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.83

.;T

M_CAP

Benign

0.030

MetaRNN

Benign

0.14

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.7

L;L

PrimateAI

Uncertain

0.78

PROVEAN

Uncertain

-2.7

D;.

REVEL

Benign

0.25

Sift

Benign

0.067

T;.

Sift4G

Uncertain

0.0080

D;D

Polyphen

0.28

B;B

Vest4

0.59

MutPred

0.17

Gain of methylation at R384 (P = 0.1098);Gain of methylation at R384 (P = 0.1098);

MVP

0.74

MPC

0.80

ClinPred

0.21

GERP RS

2.8

Varity_R

0.25

gMVP

0.20

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