Variant 1-162383208-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000458626.4(C1orf226):c.344G>A(p.Arg115Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000622 in 1,447,128 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

C1orf226
ENST00000458626.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.45

Variant links:

Genes affected

C1orf226 (HGNC:34351): (chromosome 1 open reading frame 226)

C1orf226 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.31373432).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C1orf226	NM_001085375.2 linkuse as main transcript	c.344G>A	p.Arg115Gln	missense_variant	2/2	ENST00000458626.4	NP_001078844.1
C1orf226	NM_001135240.3 linkuse as main transcript	c.473G>A	p.Arg158Gln	missense_variant	3/3		NP_001128712.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C1orf226	ENST00000458626.4 linkuse as main transcript	c.344G>A	p.Arg115Gln	missense_variant	2/2	1	NM_001085375.2	ENSP00000437071	P2	A1L170-1
C1orf226	ENST00000426197.2 linkuse as main transcript	c.473G>A	p.Arg158Gln	missense_variant	3/3	2		ENSP00000413150	A2	A1L170-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000168

AC:

AN:

238038

Hom.:

AF XY:

0.0000155

AC XY:

AN XY:

128810

show subpopulations

Gnomad AFR exome

AF:

0.0000652

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000276

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000622

AC:

AN:

1447128

Hom.:

Cov.:

AF XY:

0.00000557

AC XY:

AN XY:

718376

show subpopulations

Gnomad4 AFR exome

AF:

0.0000303

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000543

Gnomad4 OTH exome

AF:

0.0000335

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 09, 2021

The c.473G>A (p.R158Q) alteration is located in exon 3 (coding exon 3) of the C1orf226 gene. This alteration results from a G to A substitution at nucleotide position 473, causing the arginine (R) at amino acid position 158 to be replaced by a glutamine (Q). 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

0.20

BayesDel_addAF

Benign

-0.060

BayesDel_noAF

Benign

-0.14

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.40

.;.;T

Eigen

Uncertain

0.33

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.96

D;D;D

M_CAP

Benign

0.0086

MetaRNN

Benign

0.31

T;T;T

MetaSVM

Benign

-0.85

MutationAssessor

Uncertain

2.4

.;.;M

MutationTaster

Benign

0.99

N;N

PROVEAN

Uncertain

-3.8

D;D;D

REVEL

Benign

0.19

Sift

Uncertain

0.028

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0, 1.0

.;D;D

Vest4

0.68, 0.61

MutPred

0.24

Loss of phosphorylation at T112 (P = 0.1082);.;Loss of phosphorylation at T112 (P = 0.1082);

MVP

0.17

MPC

0.33

ClinPred

0.90

GERP RS

2.6

Varity_R

0.12

gMVP

0.28

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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