Genetic Variant C11orf21:p.Arg104Gln (chr11-2299544-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001329958.2(C11orf21):c.311G>A(p.Arg104Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000102 in 1,550,694 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000099 ( 0 hom. )

Consequence

C11orf21
NM_001329958.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.121

Variant links:

Genes affected

C11orf21 (HGNC:13231): (chromosome 11 open reading frame 21) Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

C11orf21 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.012851864).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C11orf21	NM_001329958.2 link	c.311G>A	p.Arg104Gln	missense_variant	Exon 3 of 4	ENST00000381153.8	NP_001316887.1	Q9P2W6
C11orf21	NM_001142946.3 link	c.449G>A	p.Arg150Gln	missense_variant	Exon 4 of 5		NP_001136418.1	Q9P2W6E9PAM5
C11orf21	NR_138249.2 link	n.423G>A		non_coding_transcript_exon_variant	Exon 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
C11orf21	ENST00000381153.8 link	c.311G>A	p.Arg104Gln	missense_variant	Exon 3 of 4	1	NM_001329958.2	ENSP00000370545.4	Q9P2W6
C11orf21	ENST00000456145.2 link	c.449G>A	p.Arg150Gln	missense_variant	Exon 4 of 5	1		ENSP00000406541.2	E9PAM5
C11orf21	ENST00000470369.1 link	n.1353G>A		non_coding_transcript_exon_variant	Exon 2 of 2	5
C11orf21	ENST00000495467.1 link	n.332G>A		non_coding_transcript_exon_variant	Exon 2 of 3	4

Frequencies

GnomAD3 genomes

AF:

0.000131

AC:

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.000967

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000109

AC:

AN:

156056

Hom.:

AF XY:

0.000133

AC XY:

AN XY:

82748

show subpopulations

Gnomad AFR exome

AF:

0.000126

Gnomad AMR exome

AF:

0.0000810

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000367

Gnomad SAS exome

AF:

0.000132

Gnomad FIN exome

AF:

0.0000603

Gnomad NFE exome

AF:

0.0000995

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000987

AC:

138

AN:

1398380

Hom.:

Cov.:

AF XY:

0.000115

AC XY:

AN XY:

689686

show subpopulations

Gnomad4 AFR exome

AF:

0.00101

Gnomad4 AMR exome

AF:

0.0000560

Gnomad4 ASJ exome

AF:

0.000119

Gnomad4 EAS exome

AF:

0.000140

Gnomad4 SAS exome

AF:

0.0000883

Gnomad4 FIN exome

AF:

0.0000621

Gnomad4 NFE exome

AF:

0.0000538

Gnomad4 OTH exome

AF:

0.000259

GnomAD4 genome

AF:

0.000131

AC:

AN:

152314

Hom.:

Cov.:

AF XY:

0.0000940

AC XY:

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.000969

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000217

Hom.:

Bravo

AF:

0.000121

ExAC

AF:

0.000156

AC:

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 06, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.449G>A (p.R150Q) alteration is located in exon 4 (coding exon 4) of the C11orf21 gene. This alteration results from a G to A substitution at nucleotide position 449, causing the arginine (R) at amino acid position 150 to be replaced by a glutamine (Q). 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

0.16

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.51

CADD

Benign

6.6

DANN

Benign

0.93

DEOGEN2

Benign

0.047

T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0095

LIST_S2

Benign

0.48

T;T

M_CAP

Benign

0.0017

MetaRNN

Benign

0.013

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;.

PROVEAN

Uncertain

-4.0

D;N

REVEL

Benign

0.042

Sift

Pathogenic

0.0

D;D

Sift4G

Benign

0.44

T;T

Polyphen

0.90

P;P

Vest4

0.11

MVP

0.17

ClinPred

0.047

GERP RS

-2.2

Varity_R

0.22

Splicing

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