NM_001329958.2:c.311G>C

Variant names:

• chr11-2299544-C-G
• rs187379934
• NM_001329958.2:c.311G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001329958.2(C11orf21):​c.311G>C​(p.Arg104Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,398,380 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R104Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: C11orf21 NM_001329958.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.121
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11223468).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001329958.2. 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
	C11orf21	NM_001329958.2	MANE Select	c.311G>C	p.Arg104Pro	missense	Exon 3 of 4	NP_001316887.1	Q9P2W6
	C11orf21	NM_001142946.3		c.449G>C	p.Arg150Pro	missense	Exon 4 of 5	NP_001136418.1	E9PAM5
	C11orf21	NR_138249.2		n.423G>C		non_coding_transcript_exon	Exon 2 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C11orf21	ENST00000381153.8	TSL:1 MANE Select	c.311G>C	p.Arg104Pro	missense	Exon 3 of 4	ENSP00000370545.4	Q9P2W6
	C11orf21	ENST00000456145.2	TSL:1	c.449G>C	p.Arg150Pro	missense	Exon 4 of 5	ENSP00000406541.2	E9PAM5
	C11orf21	ENST00000856028.1		c.311G>C	p.Arg104Pro	missense	Exon 4 of 5	ENSP00000526087.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1398380 Hom.: 0 Cov.: 31 AF XY: 0.00000145 AC XY: 1 AN XY: 689686

African (AFR) AF: 0.00 AC: 0 AN: 31596

American (AMR) AF: 0.00 AC: 0 AN: 35702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25182

East Asian (EAS) AF: 0.0000280 AC: 1 AN: 35738

South Asian (SAS) AF: 0.00 AC: 0 AN: 79236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48288

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078954

Other (OTH) AF: 0.00 AC: 0 AN: 57986

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Benign	-0.061	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	11
DANN	Benign	0.82
DEOGEN2	Benign	0.052	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.12
PROVEAN	Pathogenic	-7.0	D
REVEL	Benign	0.10
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.21	T
Polyphen		0.91	P
Vest4		0.25
MutPred		0.30		Loss of stability (P = 0.0398)
MVP		0.21
ClinPred		0.25	T
GERP RS		-2.2
Varity_R		0.49
Mutation Taster		=98/2	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs187379934; hg19: chr11-2320774;