rs527871403

Variant names:

• chr17-16046952-C-A
• NM_006311.4:c.6678G>T

Your query was ambiguous. Multiple possible variants found:

• chr17-16046952-C-A
• chr17-16046952-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006311.4(NCOR1):​c.6678G>T​(p.Met2226Ile) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NCOR1 NM_006311.4 missense, splice_region
• Scores: Splicing: ADA: 0.4266
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.55

Genes affected

NCOR1 (HGNC:7672): (nuclear receptor corepressor 1) This gene encodes a protein that mediates ligand-independent transcription repression of thyroid-hormone and retinoic-acid receptors by promoting chromatin condensation and preventing access of the transcription machinery. It is part of a complex which also includes histone deacetylases and transcriptional regulators similar to the yeast protein Sin3p. This gene is located between the Charcot-Marie-Tooth and Smith-Magenis syndrome critical regions on chromosome 17. Alternate splicing results in multiple transcript variants. Pseudogenes of this gene are found on chromosomes 17 and 20.[provided by RefSeq, Jun 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18025011).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCOR1	NM_006311.4	c.6678G>T	p.Met2226Ile	missense_variant, splice_region_variant	Exon 42 of 46	ENST00000268712.8	NP_006302.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCOR1	ENST00000268712.8	c.6678G>T	p.Met2226Ile	missense_variant, splice_region_variant	Exon 42 of 46	1	NM_006311.4	ENSP00000268712.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.45	T;.;.;T
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.92	D;D;D;D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.18	T;T;T;T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	0.81	L;.;.;.
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-1.2	N;.;N;.
REVEL	Benign	0.11
Sift	Benign	0.096	T;.;T;.
Sift4G	Benign	0.26	T;T;T;T
Polyphen		0.0050	B;.;D;.
Vest4		0.38
MutPred		0.18		Loss of catalytic residue at M2226 (P = 0.0545);.;.;.;
MVP		0.34
MPC		0.30
ClinPred		0.66	D
GERP RS		4.8
Varity_R		0.31
gMVP		0.087

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.43
dbscSNV1_RF	Benign	0.45
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: chr17-15950266; COSMIC: COSV51987458; COSMIC: COSV51987458;