Genetic Variant NM_001166692.2:c.158G>C (chr11-33700583-C-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001166692.2(C11orf91):c.158G>C(p.Gly53Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000181 in 1,458,764 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0010 ( 2 hom., cov: 33)

Exomes 𝑓: 0.000084 ( 0 hom. )

Consequence

C11orf91
NM_001166692.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.22

Publications

0 publications found

Variant links:

Genes affected

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

C11orf91 links:

ENSG00000284969 (HGNC:):

ENSG00000284969 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.031131506).

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001166692.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C11orf91	NM_001166692.2	MANE Select	c.158G>C	p.Gly53Ala	missense	Exon 1 of 2	NP_001160164.1	Q3C1V1-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
C11orf91	ENST00000379011.5	TSL:1 MANE Select	c.158G>C	p.Gly53Ala	missense	Exon 1 of 2	ENSP00000368296.4	Q3C1V1-1
ENSG00000284969	ENST00000534312.5	TSL:3	c.308-2069G>C		intron	N/A	ENSP00000432362.1
ENSG00000284969	ENST00000525763.5	TSL:3	n.*221-2069G>C		intron	N/A	ENSP00000435179.1

Frequencies

GnomAD3 genomes

AF:

0.00101

AC:

154

AN:

151984

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00369

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:

0.00

Gnomad OTH

AF:

0.000479

GnomAD2 exomes

AF:

0.0000376

AC:

AN:

79872

AF XY:

0.0000657

show subpopulations

Gnomad AFR exome

AF:

0.00106

Gnomad AMR exome

AF:

0.0000642

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000436

GnomAD4 exome

AF:

0.0000842

AC:

110

AN:

1306666

Hom.:

Cov.:

AF XY:

0.0000668

AC XY:

AN XY:

643340

show subpopulations

African (AFR)

AF:

0.00286

AC:

AN:

26944

American (AMR)

AF:

0.000226

AC:

AN:

26590

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23268

East Asian (EAS)

AF:

0.00

AC:

AN:

28080

South Asian (SAS)

AF:

0.00

AC:

AN:

69616

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32352

Middle Eastern (MID)

AF:

0.000256

AC:

AN:

3908

European-Non Finnish (NFE)

AF:

0.0000202

AC:

AN:

1041766

Other (OTH)

AF:

0.0000923

AC:

AN:

54142

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00101

AC:

154

AN:

152098

Hom.:

Cov.:

AF XY:

0.000955

AC XY:

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.00368

AC:

153

AN:

41530

American (AMR)

AF:

0.00

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5126

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10588

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67942

Other (OTH)

AF:

0.000474

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000712

Hom.:

Bravo

AF:

0.00104

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.0084

Eigen

Benign

-0.17

Eigen_PC

Benign

-0.12

FATHMM_MKL

Benign

0.33

LIST_S2

Benign

0.45

M_CAP

Pathogenic

0.87

MetaRNN

Benign

0.031

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.46

PhyloP100

1.2

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.040

Sift

Benign

0.23

Sift4G

Benign

0.42

Vest4

0.11

MVP

0.040

ClinPred

0.027

GERP RS

2.8

PromoterAI

0.093

Neutral

(source)

Varity_R

0.12

gMVP

0.15

Mutation Taster

=81/19

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over