dbSNP rs1969040922: CLIP3:p.Met288Leu (chr19-36024452-T-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_015526.3(CLIP3):c.862A>C(p.Met288Leu) variant causes a missense change. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0049 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CLIP3
NM_015526.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.22

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 Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLIP3	NM_015526.3 link	c.862A>C	p.Met288Leu	missense_variant	Exon 7 of 14	ENST00000360535.9	NP_056341.1	Q96DZ5
CLIP3	NM_001199570.2 link	c.862A>C	p.Met288Leu	missense_variant	Exon 6 of 13		NP_001186499.1	Q96DZ5
LOC101927572	NR_170987.1 link	n.385+5068T>G		intron_variant	Intron 3 of 3
LOC101927572	NR_170988.1 link	n.385+5068T>G		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CLIP3	ENST00000360535.9 link	c.862A>C	p.Met288Leu	missense_variant	Exon 7 of 14	1	NM_015526.3	ENSP00000353732.3	Q96DZ5
ENSG00000267698	ENST00000586962.1 link	n.379+5068T>G		intron_variant	Intron 3 of 3	1
CLIP3	ENST00000593074.5 link	c.862A>C	p.Met288Leu	missense_variant	Exon 6 of 13	2		ENSP00000466832.1	Q96DZ5
CLIP3	ENST00000585466.1 link	n.260A>C		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

151354

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000727

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000289

Gnomad EAS

AF:

0.000392

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000191

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00488

AC:

6866

AN:

1407742

Hom.:

Cov.:

AF XY:

0.00457

AC XY:

3210

AN XY:

701950

show subpopulations

Gnomad4 AFR exome

AF:

0.00417

Gnomad4 AMR exome

AF:

0.000430

Gnomad4 ASJ exome

AF:

0.00222

Gnomad4 EAS exome

AF:

0.00158

Gnomad4 SAS exome

AF:

0.00154

Gnomad4 FIN exome

AF:

0.000909

Gnomad4 NFE exome

AF:

0.00577

Gnomad4 OTH exome

AF:

0.00412

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000594

AC:

AN:

151472

Hom.:

Cov.:

AF XY:

0.0000811

AC XY:

AN XY:

74024

show subpopulations

Gnomad4 AFR

AF:

0.0000725

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000289

Gnomad4 EAS

AF:

0.000393

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000191

Gnomad4 NFE

AF:

0.0000148

Gnomad4 OTH

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

Sep 06, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.862A>C (p.M288L) alteration is located in exon 6 (coding exon 6) of the CLIP3 gene. This alteration results from a A to C substitution at nucleotide position 862, causing the methionine (M) at amino acid position 288 to be replaced by a leucine (L). 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

0.14

BayesDel_addAF

Pathogenic

0.16

BayesDel_noAF

Uncertain

0.0

CADD

Uncertain

DANN

Benign

0.97

DEOGEN2

Benign

0.060

T;T

Eigen

Benign

0.046

Eigen_PC

Benign

0.20

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.74

.;T

M_CAP

Benign

0.026

MetaRNN

Uncertain

0.50

D;D

MetaSVM

Benign

-0.69

MutationAssessor

Benign

2.0

M;M

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-1.5

N;.

REVEL

Uncertain

0.36

Sift

Benign

0.10

T;.

Sift4G

Benign

0.19

T;T

Polyphen

0.25

B;B

Vest4

0.64

MutPred

0.64

Loss of helix (P = 0.0068);Loss of helix (P = 0.0068);

MVP

0.85

MPC

1.1

ClinPred

0.86

GERP RS

4.9

Varity_R

0.34

gMVP

0.74

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