Genetic Variant NM_024692.6:c.131G>A (chr2-29121519-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_024692.6(CLIP4):c.131G>A(p.Cys44Tyr) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000000685 in 1,460,740 control chromosomes in the GnomAD database, with no homozygous occurrence. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CLIP4
NM_024692.6 missense, splice_region

Scores

Splicing: ADA: 0.008794

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.66

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024692.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CLIP4	NM_024692.6	MANE Select	c.131G>A	p.Cys44Tyr	missense splice_region	Exon 2 of 16	NP_078968.3
CLIP4	NM_001287527.2		c.131G>A	p.Cys44Tyr	missense splice_region	Exon 2 of 16	NP_001274456.1	Q8N3C7-1
CLIP4	NM_001287528.2		c.131G>A	p.Cys44Tyr	missense splice_region	Exon 2 of 15	NP_001274457.1	Q8N3C7-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CLIP4	ENST00000320081.10	TSL:1 MANE Select	c.131G>A	p.Cys44Tyr	missense splice_region	Exon 2 of 16	ENSP00000327009.5	Q8N3C7-1
CLIP4	ENST00000687104.1		c.-191G>A		5_prime_UTR_premature_start_codon_gain	Exon 2 of 15	ENSP00000508721.1	A0A8I5QKL4
CLIP4	ENST00000687889.1		c.-191G>A		5_prime_UTR_premature_start_codon_gain	Exon 2 of 12	ENSP00000510043.1	A0A8I5KW63

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460740

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726620

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33420

American (AMR)

AF:

0.00

AC:

AN:

44510

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26106

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39654

South Asian (SAS)

AF:

0.00

AC:

AN:

86028

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53214

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111700

Other (OTH)

AF:

0.00

AC:

AN:

60344

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

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.:

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

Uncertain

0.38

BayesDel_addAF

Pathogenic

0.31

BayesDel_noAF

Pathogenic

0.20

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.20

Eigen

Benign

0.042

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.032

MetaRNN

Uncertain

0.62

MetaSVM

Benign

-0.72

MutationAssessor

Benign

0.87

PhyloP100

5.7

PrimateAI

Pathogenic

0.80

PROVEAN

Uncertain

-3.3

REVEL

Uncertain

0.45

Sift

Benign

0.40

Sift4G

Benign

0.49

Polyphen

0.027

Vest4

0.90

MutPred

0.50

Gain of loop (P = 0.0045)

MVP

0.90

MPC

0.21

ClinPred

0.82

GERP RS

5.9

PromoterAI

-0.0025

Neutral

(source)

Varity_R

0.56

gMVP

0.85

Mutation Taster

=33/67

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0088

dbscSNV1_RF

Benign

0.10

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

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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