NM_001394591.1:c.496C>G

Variant names:

• chr1-151838494-G-C
• NM_001394591.1:c.496C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001394591.1(C2CD4D):​c.496C>G​(p.Pro166Ala) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: C2CD4D NM_001394591.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.01
• Publications: 0 publications found

Genes affected

C2CD4D (HGNC:37210): (C2 calcium dependent domain containing 4D)

C2CD4D-AS1 (HGNC:54045): (C2CD4D and THEM5 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.046303302).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394591.1. 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
	C2CD4D	NM_001394591.1	MANE Select	c.496C>G	p.Pro166Ala	missense	Exon 2 of 2	NP_001381520.1	B7Z1M9
	C2CD4D	NM_001136003.2		c.496C>G	p.Pro166Ala	missense	Exon 2 of 2	NP_001129475.1	B7Z1M9
	C2CD4D	NM_001394592.1		c.496C>G	p.Pro166Ala	missense	Exon 2 of 2	NP_001381521.1	B7Z1M9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C2CD4D	ENST00000694868.1	MANE Select	c.496C>G	p.Pro166Ala	missense	Exon 2 of 2	ENSP00000511551.1	B7Z1M9
	C2CD4D	ENST00000454109.1	TSL:2	c.496C>G	p.Pro166Ala	missense	Exon 2 of 2	ENSP00000389554.1	B7Z1M9
	C2CD4D	ENST00000694869.1		c.496C>G	p.Pro166Ala	missense	Exon 2 of 2	ENSP00000511552.1	B7Z1M9

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	13
DANN	Benign	0.57
DEOGEN2	Benign	0.0033	T
Eigen	Benign	-0.94
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.046	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.81	L
PhyloP100		1.0
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	0.15	N
REVEL	Benign	0.025
Sift	Benign	0.28	T
Sift4G	Benign	0.19	T
Polyphen		0.23	B
Vest4		0.092
MutPred		0.17		Gain of MoRF binding (P = 0.045)
MVP		0.081
ClinPred		0.12	T
GERP RS		3.3
Varity_R		0.057
gMVP		0.18
Mutation Taster		=84/16	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

hg19: chr1-151810970;