rs771007243

Variant names:

• chr2-130340913-C-A
• rs771007243
• NM_032357.4:c.425G>T

Your query was ambiguous. Multiple possible variants found:

• chr2-130340913-C-A
• chr2-130340913-C-T

Variant summary

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

The NM_032357.4(CCDC115):​c.425G>T​(p.Arg142Leu) variant causes a missense change involving the alteration of a non-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.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CCDC115 NM_032357.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.233

Genes affected

CCDC115 (HGNC:28178): (coiled-coil domain containing 115) The protein encoded by this gene has been observed to localize to the endoplasmic reticulum (ER)-Golgi intermediate compartment (ERGIC) and coat protein complex I (COPI) vesicles in some human cells. The encoded protein shares some homology with the yeast V-ATPase assembly factor Vma22p, and the orthologous protein in mouse promotes cell proliferation and suppresses cell death. Defects in this gene are a cause of congenital disorder of glycosylation, type IIo in humans. [provided by RefSeq, Mar 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC115	NM_032357.4	c.425G>T	p.Arg142Leu	missense_variant	Exon 4 of 5	ENST00000259229.7	NP_115733.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC115	ENST00000259229.7	c.425G>T	p.Arg142Leu	missense_variant	Exon 4 of 5	1	NM_032357.4	ENSP00000259229.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	T;T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.36
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.77	T;T
M_CAP	Pathogenic	0.32	D
MetaRNN	Uncertain	0.61	D;D
MetaSVM	Uncertain	0.37	D
MutationAssessor	Uncertain	2.7	M;.
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-3.6	D;D
REVEL	Uncertain	0.41
Sift	Benign	0.081	T;T
Sift4G	Benign	0.30	T;D
Polyphen		0.96	D;P
Vest4		0.45
MutPred		0.39		Loss of MoRF binding (P = 0.0056);.;
MVP		0.95
MPC		0.73
ClinPred		0.98	D
GERP RS		-0.41
Varity_R		0.077
gMVP		0.60

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: rs771007243; hg19: chr2-131098486;