rs574879223

Variant names:

• chr19-36018922-C-G
• rs574879223
• NM_015526.3:c.1159G>C

Your query was ambiguous. Multiple possible variants found:

• chr19-36018922-C-G
• chr19-36018922-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015526.3(CLIP3):​c.1159G>C​(p.Gly387Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,172 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign 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. G387S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CLIP3 NM_015526.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.90
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13395172).

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.1159G>C	p.Gly387Arg	missense	Exon 9 of 14	NP_056341.1	Q96DZ5
	CLIP3	NM_001199570.2		c.1159G>C	p.Gly387Arg	missense	Exon 8 of 13	NP_001186499.1	Q96DZ5
	LOC101927572	NR_170987.1		n.235-312C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLIP3	ENST00000360535.9	TSL:1 MANE Select	c.1159G>C	p.Gly387Arg	missense	Exon 9 of 14	ENSP00000353732.3	Q96DZ5
	ENSG00000267698	ENST00000586962.1	TSL:1	n.229-312C>G		intron	N/A
	CLIP3	ENST00000593074.5	TSL:2	c.1159G>C	p.Gly387Arg	missense	Exon 8 of 13	ENSP00000466832.1	Q96DZ5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461172 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726904

African (AFR) AF: 0.00 AC: 0 AN: 33454

American (AMR) AF: 0.00 AC: 0 AN: 44576

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26086

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86164

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53396

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111684

Other (OTH) AF: 0.00 AC: 0 AN: 60350

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.58
BayesDel_addAF	Benign	-0.032	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.057	T
Eigen	Benign	-0.21
Eigen_PC	Benign	0.00082
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	1.2	L
PhyloP100		1.9
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.12
Sift	Benign	0.038	D
Sift4G	Benign	0.10	T
Polyphen		0.0060	B
Vest4		0.40
MutPred		0.25		Loss of methylation at R390 (P = 0.0342)
MVP		0.47
MPC		0.52
ClinPred		0.80	D
GERP RS		4.9
Varity_R		0.14
gMVP		0.61
Mutation Taster		=77/23	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: rs574879223; hg19: chr19-36509824;