2-29143781-G-T

Variant names:

• chr2-29143781-G-T
• rs201519559
• NM_024692.6:c.721G>T

Variant summary

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

The NM_024692.6(CLIP4):​c.721G>T​(p.Ala241Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. A241T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CLIP4 NM_024692.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 10.0
• Publications: 0 publications found

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

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLIP4	NM_024692.6	MANE Select	c.721G>T	p.Ala241Ser	missense	Exon 7 of 16	NP_078968.3
	CLIP4	NM_001287527.2		c.721G>T	p.Ala241Ser	missense	Exon 7 of 16	NP_001274456.1	Q8N3C7-1
	CLIP4	NM_001287528.2		c.721G>T	p.Ala241Ser	missense	Exon 7 of 15	NP_001274457.1	Q8N3C7-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLIP4	ENST00000320081.10	TSL:1 MANE Select	c.721G>T	p.Ala241Ser	missense	Exon 7 of 16	ENSP00000327009.5	Q8N3C7-1
	CLIP4	ENST00000687506.1		c.721G>T	p.Ala241Ser	missense	Exon 7 of 16	ENSP00000509486.1	A0A8I5KTC6
	CLIP4	ENST00000404424.5	TSL:5	c.721G>T	p.Ala241Ser	missense	Exon 7 of 16	ENSP00000385594.1	Q8N3C7-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.49
BayesDel_addAF	Uncertain	0.087	D
BayesDel_noAF	Benign	-0.11
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.053	T
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.043	D
MetaRNN	Uncertain	0.69	D
MetaSVM	Uncertain	0.23	D
MutationAssessor	Pathogenic	3.0	M
PhyloP100		10
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-1.9	N
REVEL	Uncertain	0.41
Sift	Benign	0.045	D
Sift4G	Uncertain	0.047	D
Polyphen		1.0	D
Vest4		0.56
MutPred		0.40		Gain of catalytic residue at M237 (P = 0.0329)
MVP		0.87
MPC		0.52
ClinPred		0.97	D
GERP RS		5.5
Varity_R		0.14
gMVP		0.51
Mutation Taster		=56/44	polymorphism

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

Other links and lift over

dbSNP: rs201519559; hg19: chr2-29366647;