rs774444358

Variant names:

• chr19-36017869-C-A
• rs774444358
• NM_015526.3:c.1306G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-36017869-C-A
• chr19-36017869-C-T

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_015526.3(CLIP3):​c.1306G>T​(p.Gly436Trp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 13/22 in silico tools predict a damaging outcome for this variant. 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. G436R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CLIP3 NM_015526.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.71
• Publications: 0 publications found

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]

ENSG00000267698 (HGNC:):

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.986

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLIP3	NM_015526.3	MANE Select	c.1306G>T	p.Gly436Trp	missense	Exon 10 of 14	NP_056341.1	Q96DZ5
	CLIP3	NM_001199570.2		c.1306G>T	p.Gly436Trp	missense	Exon 9 of 13	NP_001186499.1	Q96DZ5
	LOC101927572	NR_170987.1		n.234+909C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLIP3	ENST00000360535.9	TSL:1 MANE Select	c.1306G>T	p.Gly436Trp	missense	Exon 10 of 14	ENSP00000353732.3	Q96DZ5
	ENSG00000267698	ENST00000586962.1	TSL:1	n.228+909C>A		intron	N/A
	CLIP3	ENST00000593074.5	TSL:2	c.1306G>T	p.Gly436Trp	missense	Exon 9 of 13	ENSP00000466832.1	Q96DZ5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.58	D
BayesDel_noAF	Pathogenic	0.59
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.91	D
Eigen	Pathogenic	1.0
Eigen_PC	Pathogenic	0.87
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Pathogenic	0.69	D
MetaRNN	Pathogenic	0.99	D
MetaSVM	Pathogenic	1.0	D
MutationAssessor	Pathogenic	4.8	H
PhyloP100		7.7
PrimateAI	Pathogenic	0.89	D
PROVEAN	Pathogenic	-6.7	D
REVEL	Pathogenic	0.98
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.92
MutPred		0.88		Gain of MoRF binding (P = 0.0359)
MVP		0.99
MPC		1.4
ClinPred		1.0	D
GERP RS		4.8
Varity_R		0.81
gMVP		0.79
Mutation Taster		=29/71	disease causing

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: rs774444358; hg19: chr19-36508771;