Genetic Variant CLIP1:p.Val1146Leu (chr12-122316786-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001247997.2(CLIP1):c.3436G>T(p.Val1146Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V1146I) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CLIP1
NM_001247997.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.05

Publications

0 publications found

Variant links:

Genes affected

CLIP1 (HGNC:10461): (CAP-Gly domain containing linker protein 1) The protein encoded by this gene links endocytic vesicles to microtubules. This gene is highly expressed in Reed-Sternberg cells of Hodgkin disease. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

CLIP1 Gene-Disease associations (from GenCC):

autosomal recessive non-syndromic intellectual disability
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
intellectual disability
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

CLIP1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.092378706).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001247997.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CLIP1	NM_001247997.2	MANE Select	c.3436G>T	p.Val1146Leu	missense	Exon 19 of 26	NP_001234926.1	P30622-3
CLIP1	NM_001389291.1		c.5566G>T	p.Val1856Leu	missense	Exon 18 of 25	NP_001376220.1
CLIP1	NM_002956.3		c.3403G>T	p.Val1135Leu	missense	Exon 18 of 25	NP_002947.1	P30622-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CLIP1	ENST00000620786.5	TSL:5 MANE Select	c.3436G>T	p.Val1146Leu	missense	Exon 19 of 26	ENSP00000479322.1	P30622-3
CLIP1	ENST00000358808.6	TSL:1	c.3403G>T	p.Val1135Leu	missense	Exon 18 of 25	ENSP00000351665.2	P30622-1
CLIP1	ENST00000537178.5	TSL:1	c.3298G>T	p.Val1100Leu	missense	Exon 17 of 24	ENSP00000445531.1	P30622-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1437496

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

713868

African (AFR)

AF:

0.00

AC:

AN:

32480

American (AMR)

AF:

0.00

AC:

AN:

40510

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25558

East Asian (EAS)

AF:

0.00

AC:

AN:

39096

South Asian (SAS)

AF:

0.00

AC:

AN:

79222

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53072

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5698

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1102470

Other (OTH)

AF:

0.00

AC:

AN:

59390

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.66

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.054

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.17

FATHMM_MKL

Benign

0.19

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.0029

MetaRNN

Benign

0.092

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.29

PhyloP100

1.0

PrimateAI

Uncertain

0.57

PROVEAN

Benign

0.12

REVEL

Benign

0.088

Sift

Benign

0.40

Sift4G

Benign

0.32

Polyphen

0.0

Vest4

0.14

MutPred

0.072

Loss of methylation at K1141 (P = 0.174)

MVP

0.39

MPC

0.44

ClinPred

0.90

GERP RS

5.1

Varity_R

0.037

gMVP

0.16

Mutation Taster

=95/5

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over