NM_152485.4:c.733C>G

Variant names:

• chr1-209782902-G-C
• rs757794651
• NM_152485.4:c.733C>G

Variant summary

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

The NM_152485.4(C1orf74):​c.733C>G​(p.Arg245Gly) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: C1orf74 NM_152485.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.26
• Publications: 0 publications found

Genes affected

C1orf74 (HGNC:26319): (chromosome 1 open reading frame 74)

ENSG00000289700 (HGNC:):

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=0.11863488).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152485.4. 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
	C1orf74	NM_152485.4	MANE Select	c.733C>G	p.Arg245Gly	missense	Exon 2 of 2	NP_689698.1	Q96LT6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1orf74	ENST00000294811.2	TSL:1 MANE Select	c.733C>G	p.Arg245Gly	missense	Exon 2 of 2	ENSP00000294811.1	Q96LT6
	ENSG00000289700	ENST00000696133.1		c.*747C>G		3_prime_UTR	Exon 10 of 10	ENSP00000512426.1	A0A8Q3SJ75
	C1orf74	ENST00000885064.1		c.733C>G	p.Arg245Gly	missense	Exon 2 of 2	ENSP00000555123.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

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	0.14
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.23
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		1.3
PROVEAN	Uncertain	-3.7	D
REVEL	Benign	0.073
Sift	Benign	0.11	T
Sift4G	Benign	0.19	T
Polyphen		0.018	B
Vest4		0.14
MutPred		0.28		Loss of stability (P = 0.0311)
MVP		0.31
MPC		0.82
ClinPred		0.93	D
GERP RS		4.8
Varity_R		0.19
gMVP		0.61
Mutation Taster		=93/7	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: rs757794651; hg19: chr1-209956247;