Genetic Variant C1orf174:p.Gly147Arg (chr1-3890748-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_207356.3(C1orf174):c.439G>A(p.Gly147Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00101 in 1,614,084 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00080 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0010 ( 0 hom. )

Consequence

C1orf174
NM_207356.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.00100

Variant links:

Genes affected

C1orf174 (HGNC:27915): (chromosome 1 open reading frame 174) Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

C1orf174 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.008393645).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C1orf174	NM_207356.3 link	c.439G>A	p.Gly147Arg	missense_variant	Exon 3 of 4	ENST00000361605.4	NP_997239.2	Q8IYL3
C1orf174	XM_011541323.3 link	c.472G>A	p.Gly158Arg	missense_variant	Exon 4 of 5		XP_011539625.1
C1orf174	XM_047419221.1 link	c.*254G>A		downstream_gene_variant			XP_047275177.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C1orf174	ENST00000361605.4 link	c.439G>A	p.Gly147Arg	missense_variant	Exon 3 of 4	1	NM_207356.3	ENSP00000355306.3		Q8IYL3

Frequencies

GnomAD3 genomes

AF:

0.000802

AC:

122

AN:

152096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00157

Gnomad OTH

AF:

0.000958

GnomAD3 exomes

AF:

0.000668

AC:

168

AN:

251478

Hom.:

AF XY:

0.000699

AC XY:

AN XY:

135916

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.00134

Gnomad OTH exome

AF:

0.000814

GnomAD4 exome

AF:

0.00103

AC:

1505

AN:

1461870

Hom.:

Cov.:

AF XY:

0.00101

AC XY:

734

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.000269

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.000187

Gnomad4 NFE exome

AF:

0.00130

Gnomad4 OTH exome

AF:

0.000596

GnomAD4 genome

AF:

0.000802

AC:

122

AN:

152214

Hom.:

Cov.:

AF XY:

0.000605

AC XY:

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.000217

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.00157

Gnomad4 OTH

AF:

0.000948

Alfa

AF:

0.00121

Hom.:

Bravo

AF:

0.000763

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00234

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00140

AC:

ExAC

AF:

0.000610

AC:

EpiCase

AF:

0.00104

EpiControl

AF:

0.00148

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 09, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.439G>A (p.G147R) alteration is located in exon 3 (coding exon 3) of the C1orf174 gene. This alteration results from a G to A substitution at nucleotide position 439, causing the glycine (G) at amino acid position 147 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.70

CADD

Benign

DANN

Benign

0.87

DEOGEN2

Benign

0.0056

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.037

LIST_S2

Benign

0.39

M_CAP

Benign

0.0042

MetaRNN

Benign

0.0084

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.2

PROVEAN

Benign

-0.91

REVEL

Benign

0.031

Sift

Benign

0.077

Sift4G

Benign

0.24

Polyphen

0.22

Vest4

0.10

MutPred

0.18

Gain of MoRF binding (P = 0.0098);

MVP

0.14

MPC

0.28

ClinPred

0.0027

GERP RS

-3.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.13

gMVP

0.070

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over