NM_001394591.1:c.439G>A

Variant names:

• chr1-151838551-C-T
• rs1652657457
• NM_001394591.1:c.439G>A

Variant summary

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

The NM_001394591.1(C2CD4D):​c.439G>A​(p.Asp147Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000256 in 1,170,620 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000026 (0 hom.)
• Consequence: C2CD4D NM_001394591.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.05
• 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: 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=0.23258787).

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.439G>A	p.Asp147Asn	missense	Exon 2 of 2	NP_001381520.1	B7Z1M9
	C2CD4D	NM_001136003.2		c.439G>A	p.Asp147Asn	missense	Exon 2 of 2	NP_001129475.1	B7Z1M9
	C2CD4D	NM_001394592.1		c.439G>A	p.Asp147Asn	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.439G>A	p.Asp147Asn	missense	Exon 2 of 2	ENSP00000511551.1	B7Z1M9
	C2CD4D	ENST00000454109.1	TSL:2	c.439G>A	p.Asp147Asn	missense	Exon 2 of 2	ENSP00000389554.1	B7Z1M9
	C2CD4D	ENST00000694869.1		c.439G>A	p.Asp147Asn	missense	Exon 2 of 2	ENSP00000511552.1	B7Z1M9

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000256 AC: 3 AN: 1170620 Hom.: 0 Cov.: 32 AF XY: 0.00000177 AC XY: 1 AN XY: 565656

African (AFR) AF: 0.00 AC: 0 AN: 23552

American (AMR) AF: 0.00 AC: 0 AN: 9624

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16072

East Asian (EAS) AF: 0.000112 AC: 3 AN: 26850

South Asian (SAS) AF: 0.00 AC: 0 AN: 43298

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27378

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3420

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 972882

Other (OTH) AF: 0.00 AC: 0 AN: 47544

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.18
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.082	T
Eigen	Uncertain	0.21
Eigen_PC	Benign	0.21
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.052	D
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	M
PhyloP100		5.0
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.081
Sift	Uncertain	0.018	D
Sift4G	Benign	0.11	T
Polyphen		0.91	P
Vest4		0.11
MutPred		0.14		Gain of glycosylation at P146 (P = 0.1096)
MVP		0.12
ClinPred		0.93	D
GERP RS		3.5
Varity_R		0.16
gMVP		0.25
Mutation Taster		=92/8	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: rs1652657457; hg19: chr1-151811027;