11-10752702-G-C

Position:

• chr11-10752702-G-C

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM1 PM2 PP2 PP5_Moderate

The NM_014633.5(CTR9):​c.76G>C​(p.Glu26Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CTR9 NM_014633.5 missense
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 9.60

Genes affected

CTR9 (HGNC:16850): (CTR9 homolog, Paf1/RNA polymerase II complex component) The protein encoded by this gene is a component of the PAF1 complex, which associates with RNA polymerase II and functions in transcriptional regulation and elongation. This complex also plays a role in the modification of histones. [provided by RefSeq, Oct 2016]

ACMG classification

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

• PM1: In a hotspot region, there are 3 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 3 uncertain in NM_014633.5
• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, CTR9
• PP5: Variant 11-10752702-G-C is Pathogenic according to our data. Variant chr11-10752702-G-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1173023.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTR9	NM_014633.5	c.76G>C	p.Glu26Gln	missense_variant	2/25	ENST00000361367.7
CTR9	NM_001346279.2	c.76G>C	p.Glu26Gln	missense_variant	2/24

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTR9	ENST00000361367.7	c.76G>C	p.Glu26Gln	missense_variant	2/25	1	NM_014633.5	P1
CTR9	ENST00000524523.1	c.37G>C	p.Glu13Gln	missense_variant	2/8	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

CTR9-related neurodevelopmental disorder Pathogenic:1

Likely pathogenic, criteria provided, single submitter

research

Centre of Medical Genetics, University of Antwerp

Apr 01, 2021

PS2, PM2, PP3 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.63
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.070
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T;T
Eigen	Uncertain	0.62
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D;D
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.54	D;D
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.7	L;.
MutationTaster	Benign	1.0	D
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-1.9	N;N
REVEL	Benign	0.24
Sift	Uncertain	0.0080	D;D
Sift4G	Uncertain	0.0050	D;D
Polyphen		0.93	P;.
Vest4		0.76
MutPred		0.53		Loss of disorder (P = 0.1511);.;
MVP		0.73
MPC		2.0
ClinPred		0.87	D
GERP RS		5.8
Varity_R		0.40
gMVP		0.40

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-10774249;