Variant chr11-33700622-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001166692.2(C11orf91):c.119A>G(p.Asn40Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000133 in 1,475,568 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

C11orf91
NM_001166692.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.03

Variant links:

Genes affected

C11orf91 (HGNC:34444): (chromosome 11 open reading frame 91)

C11orf91 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1399248).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C11orf91	NM_001166692.2 linkuse as main transcript	c.119A>G	p.Asn40Ser	missense_variant	1/2	ENST00000379011.5	NP_001160164.1
C11orf91	XM_017017053.2 linkuse as main transcript	c.119A>G	p.Asn40Ser	missense_variant	2/3		XP_016872542.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C11orf91	ENST00000379011.5 linkuse as main transcript	c.119A>G	p.Asn40Ser	missense_variant	1/2	1	NM_001166692.2	ENSP00000368296	P1	Q3C1V1-1

Frequencies

GnomAD3 genomes

AF:

0.0000922

AC:

AN:

151890

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000484

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:

0.00

Gnomad NFE

AF:

0.000177

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000806

AC:

AN:

86844

Hom.:

AF XY:

0.000102

AC XY:

AN XY:

49048

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.000478

Gnomad NFE exome

AF:

0.000127

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000137

AC:

182

AN:

1323678

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

105

AN XY:

652158

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000350

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000915

Gnomad4 NFE exome

AF:

0.000159

Gnomad4 OTH exome

AF:

0.000200

GnomAD4 genome

AF:

0.0000922

AC:

AN:

151890

Hom.:

Cov.:

AF XY:

0.0000809

AC XY:

AN XY:

74180

show subpopulations

Gnomad4 AFR

AF:

0.0000484

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:

0.000177

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000117

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

Jun 18, 2021

The c.119A>G (p.N40S) alteration is located in exon 1 (coding exon 1) of the C11orf91 gene. This alteration results from a A to G substitution at nucleotide position 119, causing the asparagine (N) at amino acid position 40 to be replaced by a serine (S). 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

0.11

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.085

Eigen

Benign

0.011

Eigen_PC

Benign

0.071

FATHMM_MKL

Benign

0.33

LIST_S2

Benign

0.57

M_CAP

Pathogenic

0.66

MetaRNN

Benign

0.14

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.90

MutationTaster

Benign

0.81

N;N;D;D

PROVEAN

Benign

-2.2

REVEL

Benign

0.038

Sift

Benign

0.20

Sift4G

Benign

0.47

Vest4

0.24

MVP

0.072

ClinPred

0.20

GERP RS

3.8

Varity_R

0.24

gMVP

0.15

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