chr1-151837935-C-T

Variant names:

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

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>A​(p.Ser352Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,214 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 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: 𝑓 0.0000066 (0 hom., 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=0.09033358).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C2CD4D	NM_001394591.1	c.1055G>A	p.Ser352Asn	missense_variant	Exon 2 of 2	ENST00000694868.1	NP_001381520.1
C2CD4D	NM_001136003.2	c.1055G>A	p.Ser352Asn	missense_variant	Exon 2 of 2		NP_001129475.1
C2CD4D	NM_001394592.1	c.1055G>A	p.Ser352Asn	missense_variant	Exon 2 of 2		NP_001381521.1
C2CD4D	NM_001394593.1	c.1055G>A	p.Ser352Asn	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>A	p.Ser352Asn	missense_variant	Exon 2 of 2		NM_001394591.1	ENSP00000511551.1
C2CD4D	ENST00000454109.1	c.1055G>A	p.Ser352Asn	missense_variant	Exon 2 of 2	2		ENSP00000389554.1
C2CD4D	ENST00000694869.1	c.1055G>A	p.Ser352Asn	missense_variant	Exon 2 of 2			ENSP00000511552.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152214 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000289

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152214 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74360

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.000289

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	21
DANN	Uncertain	0.97
DEOGEN2	Benign	0.0073	T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.090	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.1	L
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.49	N
REVEL	Benign	0.062
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.075	B
Vest4		0.15
MutPred		0.13		Loss of glycosylation at S352 (P = 0.0342);
MVP		0.040
ClinPred		0.48	T
GERP RS		1.9
Varity_R		0.21
gMVP		0.45

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;