Variant 1-1085922-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_017891.5(C1orf159):c.401A>G(p.Lys134Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000834 in 1,613,184 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00059 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00086 ( 2 hom. )

Consequence

C1orf159
NM_017891.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.26

Variant links:

Genes affected

C1orf159 (HGNC:26062): (chromosome 1 open reading frame 159) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

C1orf159 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.16200694).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
C1orf159	NM_017891.5 linkuse as main transcript	c.401A>G	p.Lys134Arg	missense_variant	7/10	ENST00000421241.7
C1orf159	NM_001330306.2 linkuse as main transcript	c.509A>G	p.Lys170Arg	missense_variant	9/12
C1orf159	NM_001363525.2 linkuse as main transcript	c.401A>G	p.Lys134Arg	missense_variant	8/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C1orf159	ENST00000421241.7 linkuse as main transcript	c.401A>G	p.Lys134Arg	missense_variant	7/10	2	NM_017891.5	P1	Q96HA4-4

Frequencies

GnomAD3 genomes

AF:

0.000592

AC:

AN:

152048

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000927

Gnomad OTH

AF:

0.000959

GnomAD3 exomes

AF:

0.000519

AC:

130

AN:

250350

Hom.:

AF XY:

0.000501

AC XY:

AN XY:

135596

show subpopulations

Gnomad AFR exome

AF:

0.0000618

Gnomad AMR exome

AF:

0.000897

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:

0.000833

Gnomad OTH exome

AF:

0.000654

GnomAD4 exome

AF:

0.000860

AC:

1256

AN:

1461136

Hom.:

Cov.:

AF XY:

0.000821

AC XY:

597

AN XY:

726874

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.000872

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000189

Gnomad4 NFE exome

AF:

0.00106

Gnomad4 OTH exome

AF:

0.000563

GnomAD4 genome

AF:

0.000592

AC:

AN:

152048

Hom.:

Cov.:

AF XY:

0.000458

AC XY:

AN XY:

74282

show subpopulations

Gnomad4 AFR

AF:

0.000217

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000927

Gnomad4 OTH

AF:

0.000959

Alfa

AF:

0.000750

Hom.:

Bravo

AF:

0.000706

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.000379

AC:

EpiCase

AF:

0.000818

EpiControl

AF:

0.000949

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

Mar 07, 2024

The c.401A>G (p.K134R) alteration is located in exon 7 (coding exon 5) of the C1orf159 gene. This alteration results from a A to G substitution at nucleotide position 401, causing the lysine (K) at amino acid position 134 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

0.29

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Uncertain

0.020

Cadd

Uncertain

Dann

Uncertain

1.0

DEOGEN2

Benign

0.34

T;.;.;.;T

Eigen

Benign

0.089

Eigen_PC

Benign

-0.012

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.79

T;.;T;T;T

M_CAP

Benign

0.023

MetaRNN

Benign

0.16

T;T;T;T;T

MetaSVM

Benign

-0.43

MutationAssessor

Uncertain

2.8

M;.;.;.;.

MutationTaster

Benign

0.97

D;D;D;D;D;D;D

PROVEAN

Uncertain

-3.0

D;D;D;D;D

REVEL

Benign

0.24

Sift

Pathogenic

0.0

D;D;D;D;D

Sift4G

Benign

0.081

T;D;T;D;.

Polyphen

1.0

D;D;D;D;D

Vest4

0.24

MVP

0.095

MPC

0.14

ClinPred

0.10

GERP RS

3.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.68

gMVP

0.60

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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