11-63818844-C-T

Variant summary

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

The NM_138471.3(SPINDOC):c.776C>T(p.Pro259Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SPINDOC NM_138471.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.73

Genes affected

SPINDOC (HGNC:25115): (spindlin interactor and repressor of chromatin binding) Involved in negative regulation of transcription, DNA-templated. [provided by Alliance of Genome Resources, Apr 2022]

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/exons	MANE	UniProt
SPINDOC	NM_138471.3	c.776C>T	p.Pro259Leu	missense_variant	5/6	ENST00000294244.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPINDOC	ENST00000294244.9	c.776C>T	p.Pro259Leu	missense_variant	5/6	1	NM_138471.3	P1
SPINDOC	ENST00000540893.1	c.101C>T	p.Pro34Leu	missense_variant	2/4	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 06, 2021

The c.776C>T (p.P259L) alteration is located in exon 5 (coding exon 5) of the C11orf84 gene. This alteration results from a C to T substitution at nucleotide position 776, causing the proline (P) at amino acid position 259 to be replaced by a leucine (L). 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	0.077	D
BayesDel_noAF	Benign	-0.13
Cadd	Uncertain	26
Dann	Pathogenic	1.0
DEOGEN2	Benign	0.17	T;.
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.86	D;D
M_CAP	Uncertain	0.098	D
MetaRNN	Uncertain	0.61	D;D
MetaSVM	Uncertain	-0.17	T
MutationTaster	Benign	1.0	D
PROVEAN	Uncertain	-2.9	D;D
REVEL	Uncertain	0.30
Sift	Uncertain	0.0080	D;D
Sift4G	Uncertain	0.021	D;D
Polyphen		1.0	D;.
Vest4		0.75
MutPred		0.39		Gain of helix (P = 0.0034);.;
MVP		0.82
MPC		0.98
ClinPred		0.89	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.094
gMVP		0.34

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: chr11-63586316;