11-68262469-G-A

Variant names:

• chr11-68262469-G-A
• rs146708926
• NM_022338.4:c.526C>T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_022338.4(C11orf24):​c.526C>T​(p.Arg176Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00123 in 1,614,096 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R176Q) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00088 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0013 (0 hom.)
• Consequence: C11orf24 NM_022338.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.302

Genes affected

C11orf24 (HGNC:1174): (chromosome 11 open reading frame 24) Located in Golgi apparatus and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0075229704).
• BP6: Variant 11-68262469-G-A is Benign according to our data. Variant chr11-68262469-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2378429.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C11orf24	NM_022338.4	c.526C>T	p.Arg176Trp	missense_variant	Exon 4 of 4	ENST00000304271.11	NP_071733.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C11orf24	ENST00000304271.11	c.526C>T	p.Arg176Trp	missense_variant	Exon 4 of 4	1	NM_022338.4	ENSP00000307264.6
C11orf24	ENST00000533310.5	c.264+262C>T		intron_variant	Intron 4 of 4	5		ENSP00000434144.1
C11orf24	ENST00000530166.5	n.935C>T		non_coding_transcript_exon_variant	Exon 4 of 4	3
C11orf24	ENST00000531745.1	n.112-667C>T		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes AF: 0.000880 AC: 134 AN: 152208 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00255

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00122

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.000750 AC: 188 AN: 250632 Hom.: 0 AF XY: 0.000744 AC XY: 101 AN XY: 135664

Gnomad AFR exome AF: 0.0000617

Gnomad AMR exome AF: 0.00124

Gnomad ASJ exome AF: 0.0000996

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000163

Gnomad FIN exome AF: 0.0000463

Gnomad NFE exome AF: 0.00116

Gnomad OTH exome AF: 0.000982

GnomAD4 exome AF: 0.00127 AC: 1850 AN: 1461770 Hom.: 0 Cov.: 59 AF XY: 0.00122 AC XY: 886 AN XY: 727192

Gnomad4 AFR exome AF: 0.000179

Gnomad4 AMR exome AF: 0.00112

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000383

Gnomad4 FIN exome AF: 0.0000375

Gnomad4 NFE exome AF: 0.00152

Gnomad4 OTH exome AF: 0.00111

GnomAD4 genome AF: 0.000880 AC: 134 AN: 152326 Hom.: 0 Cov.: 33 AF XY: 0.00105 AC XY: 78 AN XY: 74492

Gnomad4 AFR AF: 0.000144

Gnomad4 AMR AF: 0.00255

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.00122

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.000972 Hom.: 0

Bravo AF: 0.000982

TwinsUK AF: 0.00135 AC: 5

ALSPAC AF: 0.00311 AC: 12

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000815 AC: 7

ExAC AF: 0.000610 AC: 74

Asia WGS AF: 0.000578 AC: 2 AN: 3476

EpiCase AF: 0.00131

EpiControl AF: 0.00113

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Jun 22, 2021

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	13
DANN	Benign	0.89
DEOGEN2	Benign	0.0031	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.084	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.0075	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PROVEAN	Benign	-0.67	N
REVEL	Benign	0.050
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.017	D
Polyphen		0.0030	B
Vest4		0.059
MVP		0.014
MPC		0.051
ClinPred		0.0098	T
GERP RS		-1.8
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0
Varity_R		0.046
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

Other links and lift over

dbSNP: rs146708926; hg19: chr11-68029937; COSMIC: COSV105162448; COSMIC: COSV105162448;