chr2-29121479-G-A

Position:

• chr2-29121479-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024692.6(CLIP4):​c.91G>A​(p.Val31Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: CLIP4 NM_024692.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.78

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26031375).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLIP4	NM_024692.6	c.91G>A	p.Val31Ile	missense_variant	2/16	ENST00000320081.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLIP4	ENST00000320081.10	c.91G>A	p.Val31Ile	missense_variant	2/16	1	NM_024692.6	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 23, 2023

The c.91G>A (p.V31I) alteration is located in exon 2 (coding exon 1) of the CLIP4 gene. This alteration results from a G to A substitution at nucleotide position 91, causing the valine (V) at amino acid position 31 to be replaced by an isoleucine (I). 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	0.080
BayesDel_addAF	Uncertain	0.053	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.022	.;T;T;.
Eigen	Benign	0.043
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.83	T;.;T;T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.26	T;T;T;T
MetaSVM	Benign	-0.44	T
MutationAssessor	Benign	1.5	L;L;L;.
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.37	N;N;N;N
REVEL	Benign	0.24
Sift	Benign	0.062	T;D;D;D
Sift4G	Uncertain	0.058	T;T;T;T
Polyphen		0.052	.;B;B;.
Vest4		0.34
MutPred		0.23		Loss of catalytic residue at V31 (P = 0.0295);Loss of catalytic residue at V31 (P = 0.0295);Loss of catalytic residue at V31 (P = 0.0295);Loss of catalytic residue at V31 (P = 0.0295);
MVP		0.77
MPC		0.12
ClinPred		0.85	D
GERP RS		6.0
Varity_R		0.097
gMVP		0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-29344345; COSMIC: COSV60748314; COSMIC: COSV60748314;