Genetic Variant NM_015526.3:c.1166G>C (chr19-36018915-C-G) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_015526.3(CLIP3):c.1166G>C(p.Gly389Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,232 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G389D) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

CLIP3
NM_015526.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.11

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.08165184).

BS2

High AC in GnomAdExome4 at 7 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015526.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CLIP3	NM_015526.3	MANE Select	c.1166G>C	p.Gly389Ala	missense	Exon 9 of 14	NP_056341.1	Q96DZ5
CLIP3	NM_001199570.2		c.1166G>C	p.Gly389Ala	missense	Exon 8 of 13	NP_001186499.1	Q96DZ5
LOC101927572	NR_170987.1		n.235-319C>G		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CLIP3	ENST00000360535.9	TSL:1 MANE Select	c.1166G>C	p.Gly389Ala	missense	Exon 9 of 14	ENSP00000353732.3	Q96DZ5
ENSG00000267698	ENST00000586962.1	TSL:1	n.229-319C>G		intron	N/A
CLIP3	ENST00000593074.5	TSL:2	c.1166G>C	p.Gly389Ala	missense	Exon 8 of 13	ENSP00000466832.1	Q96DZ5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000798

AC:

AN:

250614

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000883

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461232

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726930

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33454

American (AMR)

AF:

0.00

AC:

AN:

44586

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26086

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86164

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53400

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00000540

AC:

AN:

1111728

Other (OTH)

AF:

0.00

AC:

AN:

60354

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.0000165

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.090

BayesDel_noAF

Benign

-0.27

CADD

Benign

(source)

DANN

Benign

0.84

DEOGEN2

Benign

0.024

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.059

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.74

M_CAP

Benign

0.022

MetaRNN

Benign

0.082

MetaSVM

Benign

-0.84

MutationAssessor

Benign

0.90

PhyloP100

3.1

PrimateAI

Uncertain

0.68

PROVEAN

Benign

0.020

REVEL

Benign

0.15

Sift

Benign

0.87

Sift4G

Benign

0.43

Polyphen

0.13

Vest4

0.52

MutPred

0.20

Loss of sheet (P = 0.0483)

MVP

0.60

MPC

0.46

ClinPred

0.21

GERP RS

4.9

Varity_R

0.072

gMVP

0.41

Mutation Taster

=92/8

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over