1-35715814-C-G

Variant names:

• chr1-35715814-C-G
• rs369687783
• NM_152374.2:c.508G>C

Variant summary

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

The NM_152374.2(C1orf216):​c.508G>C​(p.Val170Leu) 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. V170M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: C1orf216 NM_152374.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.94
• Publications: 0 publications found

Genes affected

C1orf216 (HGNC:26800): (chromosome 1 open reading frame 216)

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=0.080497265).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152374.2. 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
	C1orf216	NM_152374.2	MANE Select	c.508G>C	p.Val170Leu	missense	Exon 2 of 2	NP_689587.1	Q8TAB5
	C1orf216	NM_001348691.2		c.508G>C	p.Val170Leu	missense	Exon 2 of 2	NP_001335620.1	Q8TAB5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1orf216	ENST00000270815.5	TSL:1 MANE Select	c.508G>C	p.Val170Leu	missense	Exon 2 of 2	ENSP00000425166.1	Q8TAB5
	C1orf216	ENST00000856968.1		c.508G>C	p.Val170Leu	missense	Exon 2 of 2	ENSP00000527027.1
	C1orf216	ENST00000856969.1		c.508G>C	p.Val170Leu	missense	Exon 2 of 2	ENSP00000527028.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.077	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	16
DANN	Benign	0.97
DEOGEN2	Benign	0.035	T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.55	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.0060	T
MetaRNN	Benign	0.080	T
MetaSVM	Benign	-0.75	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		1.9
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.026
Sift	Benign	0.035	D
Sift4G	Benign	0.069	T
Polyphen		0.13	B
Vest4		0.26
MutPred		0.27		Loss of methylation at K165 (P = 0.068)
MVP		0.59
MPC		0.22
ClinPred		0.67	D
GERP RS		2.7
Varity_R		0.19
gMVP		0.091
Mutation Taster		=98/2	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: rs369687783; hg19: chr1-36181415;