1-151838415-G-T

Variant names:

• chr1-151838415-G-T
• rs368203330
• NM_001394591.1:c.575C>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.575C>A​(p.Pro192Gln) 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. 13/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. P192L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: C2CD4D NM_001394591.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.48
• 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=0.23741841).

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.575C>A	p.Pro192Gln	missense	Exon 2 of 2	NP_001381520.1	B7Z1M9
	C2CD4D	NM_001136003.2		c.575C>A	p.Pro192Gln	missense	Exon 2 of 2	NP_001129475.1	B7Z1M9
	C2CD4D	NM_001394592.1		c.575C>A	p.Pro192Gln	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.575C>A	p.Pro192Gln	missense	Exon 2 of 2	ENSP00000511551.1	B7Z1M9
	C2CD4D	ENST00000454109.1	TSL:2	c.575C>A	p.Pro192Gln	missense	Exon 2 of 2	ENSP00000389554.1	B7Z1M9
	C2CD4D	ENST00000694869.1		c.575C>A	p.Pro192Gln	missense	Exon 2 of 2	ENSP00000511552.1	B7Z1M9

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1278860 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 629202

African (AFR) AF: 0.00 AC: 0 AN: 25592

American (AMR) AF: 0.00 AC: 0 AN: 19502

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21380

East Asian (EAS) AF: 0.00 AC: 0 AN: 27496

South Asian (SAS) AF: 0.00 AC: 0 AN: 65226

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35368

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4902

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1026804

Other (OTH) AF: 0.00 AC: 0 AN: 52590

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	23
DANN	Benign	0.97
DEOGEN2	Benign	0.023	T
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		1.5
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.074
Sift	Benign	0.13	T
Sift4G	Benign	0.19	T
Polyphen		1.0	D
Vest4		0.15
MutPred		0.20		Loss of glycosylation at P192 (P = 0.0118)
MVP		0.24
ClinPred		0.79	D
GERP RS		3.1
Varity_R		0.084
gMVP		0.42
Mutation Taster		=86/14	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: rs368203330; hg19: chr1-151810891; COSMIC: COSV63256188; COSMIC: COSV63256188;