1-151837935-C-G

Variant names:

• chr1-151837935-C-G
• rs375839900
• NM_001394591.1:c.1055G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001394591.1(C2CD4D):​c.1055G>C​(p.Ser352Thr) 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. 14/20 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. S352I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: C2CD4D NM_001394591.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.806

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13152757).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C2CD4D	NM_001394591.1	c.1055G>C	p.Ser352Thr	missense_variant	Exon 2 of 2	ENST00000694868.1	NP_001381520.1
C2CD4D	NM_001136003.2	c.1055G>C	p.Ser352Thr	missense_variant	Exon 2 of 2		NP_001129475.1
C2CD4D	NM_001394592.1	c.1055G>C	p.Ser352Thr	missense_variant	Exon 2 of 2		NP_001381521.1
C2CD4D	NM_001394593.1	c.1055G>C	p.Ser352Thr	missense_variant	Exon 2 of 2		NP_001381522.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C2CD4D	ENST00000694868.1	c.1055G>C	p.Ser352Thr	missense_variant	Exon 2 of 2		NM_001394591.1	ENSP00000511551.1
C2CD4D	ENST00000454109.1	c.1055G>C	p.Ser352Thr	missense_variant	Exon 2 of 2	2		ENSP00000389554.1
C2CD4D	ENST00000694869.1	c.1055G>C	p.Ser352Thr	missense_variant	Exon 2 of 2			ENSP00000511552.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Benign	0.0076	T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.22
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.32	T
M_CAP	Benign	0.0085	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.35	N
REVEL	Benign	0.14
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.81	P
Vest4		0.12
MutPred		0.069		Loss of phosphorylation at S352 (P = 0.1094);
MVP		0.055
ClinPred		0.39	T
GERP RS		1.9
Varity_R		0.22
gMVP		0.47

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: rs375839900; hg19: chr1-151810411;