Variant chr1-10976227-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP5BP4

The NM_001170754.2(C1orf127):c.56C>T(p.Thr19Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000432 in 1,536,352 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00046 ( 0 hom. )

Consequence

C1orf127
NM_001170754.2 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: -0.242

Variant links:

Genes affected

C1orf127 (HGNC:26730): (chromosome 1 open reading frame 127) Predicted to be involved in heart development. Predicted to act upstream of or within determination of left/right symmetry. [provided by Alliance of Genome Resources, Apr 2022]

C1orf127 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 1-10976227-G-A is Pathogenic according to our data. Variant chr1-10976227-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 3602006.Status of the report is no_assertion_criteria_provided, 0 stars.

BP4

Computational evidence support a benign effect (MetaRNN=0.06312519). . Strength limited to SUPPORTING due to the PP5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C1orf127	NM_001170754.2 link	c.56C>T	p.Thr19Met	missense_variant	2/13	ENST00000377004.9	NP_001164225.1	G8JLG8B7ZLG7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C1orf127	ENST00000377004.9 link	c.56C>T	p.Thr19Met	missense_variant	2/13	5	NM_001170754.2	ENSP00000366203.4		G8JLG8
C1orf127	ENST00000520253.1 link	c.-14C>T		upstream_gene_variant		5		ENSP00000429704.1		H0YBK5

Frequencies

GnomAD3 genomes

AF:

0.000171

AC:

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.000279

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000208

AC:

AN:

139444

Hom.:

AF XY:

0.000227

AC XY:

AN XY:

74778

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000163

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000941

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000411

Gnomad OTH exome

AF:

0.000238

GnomAD4 exome

AF:

0.000461

AC:

638

AN:

1384066

Hom.:

Cov.:

AF XY:

0.000441

AC XY:

301

AN XY:

682958

show subpopulations

Gnomad4 AFR exome

AF:

0.000190

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000280

Gnomad4 SAS exome

AF:

0.0000253

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000564

Gnomad4 OTH exome

AF:

0.000277

GnomAD4 genome

AF:

0.000171

AC:

AN:

152286

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000279

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000214

Hom.:

Bravo

AF:

0.000196

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00156

AC:

ExAC

AF:

0.0000431

AC:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

HETEROTAXY, VISCERAL, 14, AUTOSOMAL

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jan 31, 2025

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.77

CADD

Benign

7.0

DANN

Uncertain

1.0

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.87

FATHMM_MKL

Benign

0.0029

LIST_S2

Benign

0.49

M_CAP

Benign

0.0050

MetaRNN

Benign

0.063

MetaSVM

Benign

-0.97

PROVEAN

Benign

-0.19

REVEL

Benign

0.0040

Sift

Benign

0.21

Sift4G

Uncertain

0.023

Vest4

0.19

MutPred

0.33

Loss of glycosylation at T19 (P = 0.0216);

MVP

0.061

MPC

0.41

ClinPred

0.15

GERP RS

-0.94

gMVP

0.12

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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