11-109423674-C-A

Variant names:

• chr11-109423674-C-A
• rs759575149
• NM_207645.4:c.41C>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_207645.4(C11orf87):​c.41C>A​(p.Pro14Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,456,176 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: C11orf87 NM_207645.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.40

Genes affected

C11orf87 (HGNC:33788): (chromosome 11 open reading frame 87) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000255028 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C11orf87	NM_207645.4	c.41C>A	p.Pro14Gln	missense_variant	Exon 2 of 2	ENST00000327419.7	NP_997528.2
C11orf87	XM_011542817.3	c.482C>A	p.Pro161Gln	missense_variant	Exon 2 of 2		XP_011541119.1
C11orf87	XM_011542818.3	c.41C>A	p.Pro14Gln	missense_variant	Exon 2 of 2		XP_011541120.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C11orf87	ENST00000327419.7	c.41C>A	p.Pro14Gln	missense_variant	Exon 2 of 2	1	NM_207645.4	ENSP00000331581.6
ENSG00000255028	ENST00000532929.1	n.253-7503G>T		intron_variant	Intron 2 of 3	3
ENSG00000255028	ENST00000532992.5	n.428-58606G>T		intron_variant	Intron 3 of 4	4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000410 AC: 1 AN: 243998 Hom.: 0 AF XY: 0.00000754 AC XY: 1 AN XY: 132568

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: 0.0000328

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1456176 Hom.: 0 Cov.: 31 AF XY: 0.00000276 AC XY: 2 AN XY: 724592

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000825 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 12, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.41C>A (p.P14Q) alteration is located in exon 2 (coding exon 1) of the C11orf87 gene. This alteration results from a C to A substitution at nucleotide position 41, causing the proline (P) at amino acid position 14 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	Pathogenic	0.87
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	0.070
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.058	D
MetaRNN	Uncertain	0.67	D
MetaSVM	Benign	-0.48	T
MutationAssessor	Benign	0.97	L
PROVEAN	Pathogenic	-6.1	D
REVEL	Uncertain	0.43
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.76
MutPred		0.38		Gain of helix (P = 0.0117);
MVP		0.50
MPC		1.2
ClinPred		0.99	D
GERP RS		4.4
Varity_R		0.73
gMVP		0.71

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: rs759575149; hg19: chr11-109294400;