C2CD4C p.Val309Leu

Variant names:

• chr19-407437-C-A
• NM_001136263.2:c.925G>T
• C2CD4C p.Val309Leu

Your query was ambiguous. Multiple possible variants found:

• chr19-407437-C-A
• chr19-407437-C-G
• chr19-407435-CAC-TAA
• chr19-407435-CAC-AAG
• chr19-407435-CAC-GAG
• chr19-407435-CAC-TAG

Variant summary

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

The NM_001136263.2(C2CD4C):​c.925G>T​(p.Val309Leu) 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. 15/22 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: C2CD4C NM_001136263.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.678
• Publications: 0 publications found

Genes affected

C2CD4C (HGNC:29417): (C2 calcium dependent domain containing 4C) Predicted to be active in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

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=0.106575996).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001136263.2. 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
	C2CD4C	NM_001136263.2	MANE Select	c.925G>T	p.Val309Leu	missense	Exon 2 of 2	NP_001129735.1	Q8TF44

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C2CD4C	ENST00000332235.8	TSL:2 MANE Select	c.925G>T	p.Val309Leu	missense	Exon 2 of 2	ENSP00000328677.4	Q8TF44
	C2CD4C	ENST00000920287.1		c.925G>T	p.Val309Leu	missense	Exon 2 of 2	ENSP00000590346.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1339064 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 657266

African (AFR) AF: 0.00 AC: 0 AN: 29788

American (AMR) AF: 0.00 AC: 0 AN: 28818

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21836

East Asian (EAS) AF: 0.00 AC: 0 AN: 34910

South Asian (SAS) AF: 0.00 AC: 0 AN: 70660

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33962

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4576

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1058802

Other (OTH) AF: 0.00 AC: 0 AN: 55712

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	6.7
DANN	Benign	0.84
DEOGEN2	Benign	0.0096	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.65	T
M_CAP	Pathogenic	0.79	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	-1.2	N
PhyloP100		-0.68
PrimateAI	Pathogenic	0.94	D
PROVEAN	Benign	1.4	N
REVEL	Benign	0.16
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Varity_R		0.036
gMVP		0.34
Mutation Taster		=83/17	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr19-407437;