chr2-29143807-G-C

Position:

• chr2-29143807-G-C

Variant summary

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

The NM_024692.6(CLIP4):​c.747G>C​(p.Gln249His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 2.15

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLIP4	NM_024692.6	c.747G>C	p.Gln249His	missense_variant	7/16	ENST00000320081.10	NP_078968.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLIP4	ENST00000320081.10	c.747G>C	p.Gln249His	missense_variant	7/16	1	NM_024692.6	ENSP00000327009	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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

Feb 15, 2023

The c.747G>C (p.Q249H) alteration is located in exon 7 (coding exon 6) of the CLIP4 gene. This alteration results from a G to C substitution at nucleotide position 747, causing the glutamine (Q) at amino acid position 249 to be replaced by a histidine (H). 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	Uncertain	0.39
BayesDel_addAF	Uncertain	0.012	T
BayesDel_noAF	Benign	-0.22
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.074	.;.;T;T
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.94	D;D;.;D
M_CAP	Benign	0.062	D
MetaRNN	Uncertain	0.48	T;T;T;T
MetaSVM	Uncertain	0.27	D
MutationAssessor	Uncertain	2.8	M;.;M;M
MutationTaster	Benign	0.96	D;D;D;D;D
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-2.4	N;N;N;N
REVEL	Benign	0.28
Sift	Benign	0.034	D;D;D;D
Sift4G	Uncertain	0.051	T;D;D;D
Polyphen		1.0	.;.;D;D
Vest4		0.44
MutPred		0.37		Gain of catalytic residue at L251 (P = 0.0628);.;Gain of catalytic residue at L251 (P = 0.0628);Gain of catalytic residue at L251 (P = 0.0628);
MVP		0.89
MPC		0.53
ClinPred		0.94	D
GERP RS		4.6
Varity_R		0.15
gMVP		0.57

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-29366673;