NM_173648.4:c.4396G>T

Variant names:

• chr2-178834370-C-A
• rs1250247342
• NM_173648.4:c.4396G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_173648.4(CCDC141):​c.4396G>T​(p.Val1466Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 11/13 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCDC141 NM_173648.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.10

Genes affected

CCDC141 (HGNC:26821): (coiled-coil domain containing 141) Predicted to be involved in axon guidance and cell adhesion. Predicted to act upstream of or within centrosome localization and cerebral cortex radially oriented cell migration. Predicted to be located in centrosome; cytoplasm; and plasma membrane. Predicted to be active in neuron projection. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000287149 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10625127).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC141	NM_173648.4	c.4396G>T	p.Val1466Leu	missense_variant	Exon 24 of 24	ENST00000443758.7	NP_775919.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC141	ENST00000443758.7	c.4396G>T	p.Val1466Leu	missense_variant	Exon 24 of 24	5	NM_173648.4	ENSP00000390190.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	16
DANN	Benign	0.60
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.98	T
PrimateAI	Benign	0.47	T
MutPred		0.55		Gain of catalytic residue at V1466 (P = 0.0279);
ClinPred		0.18	T
GERP RS		4.9

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

LitVar

Other links and lift over

dbSNP: rs1250247342; hg19: chr2-179699097;