7-26206456-G-T

Variant names:

• chr7-26206456-G-T
• NM_016587.4:c.113G>T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_016587.4(CBX3):​c.113G>T​(p.Arg38Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,634 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CBX3 NM_016587.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.11

Genes affected

CBX3 (HGNC:1553): (chromobox 3) At the nuclear envelope, the nuclear lamina and heterochromatin are adjacent to the inner nuclear membrane. The protein encoded by this gene binds DNA and is a component of heterochromatin. This protein also can bind lamin B receptor, an integral membrane protein found in the inner nuclear membrane. The dual binding functions of the encoded protein may explain the association of heterochromatin with the inner nuclear membrane. This protein binds histone H3 tails methylated at Lys-9 sites. This protein is also recruited to sites of ultraviolet-induced DNA damage and double-strand breaks. Two transcript variants encoding the same protein but differing in the 5' UTR, have been found for this gene.[provided by RefSeq, Mar 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.767

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CBX3	NM_016587.4	c.113G>T	p.Arg38Leu	missense_variant	Exon 3 of 6	ENST00000396386.7	NP_057671.2
CBX3	NM_007276.5	c.113G>T	p.Arg38Leu	missense_variant	Exon 3 of 6		NP_009207.2
CBX3	NM_001410866.1	c.113G>T	p.Arg38Leu	missense_variant	Exon 3 of 6		NP_001397795.1
CBX3	XM_005249611.5	c.113G>T	p.Arg38Leu	missense_variant	Exon 3 of 6		XP_005249668.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CBX3	ENST00000396386.7	c.113G>T	p.Arg38Leu	missense_variant	Exon 3 of 6	1	NM_016587.4	ENSP00000379670.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461634 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 727112

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.11
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.66	D;D;D;D;.
Eigen	Uncertain	0.68
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.82	.;T;T;D;T
M_CAP	Benign	0.028	D
MetaRNN	Pathogenic	0.77	D;D;D;D;D
MetaSVM	Uncertain	0.20	D
MutationAssessor	Uncertain	2.4	M;M;.;.;.
PrimateAI	Pathogenic	0.86	D
PROVEAN	Pathogenic	-4.5	D;D;D;D;.
REVEL	Uncertain	0.63
Sift	Uncertain	0.0090	D;D;D;D;.
Sift4G	Uncertain	0.026	D;D;T;D;D
Polyphen		0.047	B;B;.;D;.
Vest4		0.77
MutPred		0.50		Loss of MoRF binding (P = 0.0298);Loss of MoRF binding (P = 0.0298);Loss of MoRF binding (P = 0.0298);Loss of MoRF binding (P = 0.0298);.;
MVP		0.85
MPC		1.3
ClinPred		0.99	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.84
gMVP		0.45

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: chr7-26246076;