chr19-36024562-G-T

Variant names:

• chr19-36024562-G-T
• NM_015526.3:c.752C>A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_015526.3(CLIP3):​c.752C>A​(p.Ala251Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000547 in 1,461,858 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: CLIP3 NM_015526.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.80

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

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLIP3	NM_015526.3	c.752C>A	p.Ala251Glu	missense_variant	Exon 7 of 14	ENST00000360535.9	NP_056341.1
CLIP3	NM_001199570.2	c.752C>A	p.Ala251Glu	missense_variant	Exon 6 of 13		NP_001186499.1
LOC101927572	NR_170987.1	n.385+5178G>T		intron_variant	Intron 3 of 3
LOC101927572	NR_170988.1	n.385+5178G>T		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLIP3	ENST00000360535.9	c.752C>A	p.Ala251Glu	missense_variant	Exon 7 of 14	1	NM_015526.3	ENSP00000353732.3
ENSG00000267698	ENST00000586962.1	n.379+5178G>T		intron_variant	Intron 3 of 3	1
CLIP3	ENST00000593074.5	c.752C>A	p.Ala251Glu	missense_variant	Exon 6 of 13	2		ENSP00000466832.1
CLIP3	ENST00000585466.1	n.150C>A		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000547 AC: 8 AN: 1461858 Hom.: 0 Cov.: 35 AF XY: 0.00000550 AC XY: 4 AN XY: 727226

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000719

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.74
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.030
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.086	T;T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.92	.;D
M_CAP	Benign	0.029	D
MetaRNN	Uncertain	0.58	D;D
MetaSVM	Benign	-0.61	T
MutationAssessor	Uncertain	2.4	M;M
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-3.0	D;.
REVEL	Uncertain	0.44
Sift	Benign	0.23	T;.
Sift4G	Benign	0.24	T;T
Polyphen		0.96	D;D
Vest4		0.79
MutPred		0.64		Gain of ubiquitination at K256 (P = 0.0662);Gain of ubiquitination at K256 (P = 0.0662);
MVP		0.70
MPC		1.4
ClinPred		0.91	D
GERP RS		5.9
Varity_R		0.41
gMVP		0.90

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: chr19-36515464;