11-93759857-C-T

Position:

chr11-93759857-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001286069.2(C11orf54):c.773C>T(p.Pro258Leu) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000142 in 1,552,274 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

C11orf54
NM_001286069.2 missense, splice_region

Scores

Splicing: ADA: 0.9940

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.31

Variant links:

Genes affected

C11orf54 (HGNC:30204): (chromosome 11 open reading frame 54) Enables hydrolase activity, acting on ester bonds and zinc ion binding activity. Located in nuclear body. [provided by Alliance of Genome Resources, Apr 2022]

C11orf54 links:

ENSG00000284057 (HGNC:):

ENSG00000284057 links:

TAF1D (HGNC:28759): (TATA-box binding protein associated factor, RNA polymerase I subunit D) TAF1D is a member of the SL1 complex, which includes TBP (MIM 600075) and TAF1A (MIM 604903), TAF1B (MIM 604904), and TAF1C (MIM 604905), and plays a role in RNA polymerase I transcription (Wang et al., 2004 [PubMed 15520167]; Gorski et al., 2007 [PubMed 17318177]).[supplied by OMIM, Jun 2009]

TAF1D links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.79

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C11orf54	NM_001286069.2 linkuse as main transcript	c.773C>T	p.Pro258Leu	missense_variant, splice_region_variant	8/9	ENST00000354421.8	NP_001272998.1	Q9H0W9-1A0A024R396A8K718

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C11orf54	ENST00000354421.8 linkuse as main transcript	c.773C>T	p.Pro258Leu	missense_variant, splice_region_variant	8/9	1	NM_001286069.2	ENSP00000346403.3		Q9H0W9-1
ENSG00000284057	ENST00000638767.1 linkuse as main transcript	c.674C>T	p.Pro225Leu	missense_variant, splice_region_variant	7/19	5		ENSP00000492220.1		A0A1W2PRB8

Frequencies

GnomAD3 genomes

AF:

0.000118

AC:

AN:

152064

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000411

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000162

AC:

AN:

247340

Hom.:

AF XY:

0.0000149

AC XY:

AN XY:

133798

show subpopulations

Gnomad AFR exome

AF:

0.000248

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000286

AC:

AN:

1400092

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

699316

show subpopulations

Gnomad4 AFR exome

AF:

0.0000625

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:

0.00000188

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.000118

AC:

AN:

152182

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.000409

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000331

Hom.:

Bravo

AF:

0.0000869

ExAC

AF:

0.0000330

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

Aug 16, 2021

The c.623C>T (p.P208L) alteration is located in exon 7 (coding exon 6) of the C11orf54 gene. This alteration results from a C to T substitution at nucleotide position 623, causing the proline (P) at amino acid position 208 to be replaced by a leucine (L). 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

0.22

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Pathogenic

0.30

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

.;.;.;T;T;T;.;.;.

Eigen

Pathogenic

1.1

Eigen_PC

Pathogenic

0.96

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.97

D;D;D;.;.;D;D;D;D

M_CAP

Benign

0.014

MetaRNN

Uncertain

0.74

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

MetaSVM

Benign

-0.48

MutationAssessor

Uncertain

2.1

.;.;.;M;M;M;.;.;.

PROVEAN

Pathogenic

-6.2

D;.;D;D;D;D;D;D;.

REVEL

Pathogenic

0.73

Sift

Benign

0.090

T;.;T;T;T;T;D;T;.

Sift4G

Benign

0.56

T;T;T;T;T;T;D;T;.

Polyphen

0.98

D;.;.;D;D;D;.;.;.

Vest4

0.93

MutPred

0.71

.;.;.;Loss of disorder (P = 0.0707);Loss of disorder (P = 0.0707);Loss of disorder (P = 0.0707);.;.;.;

MVP

0.71

MPC

0.27

ClinPred

0.56

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.48

gMVP

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.99

dbscSNV1_RF

Pathogenic

0.89

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