16-24561981-T-G

Variant names:

• chr16-24561981-T-G
• NM_006910.5:c.1109T>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006910.5(RBBP6):​c.1109T>G​(p.Met370Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,682 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: RBBP6 NM_006910.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.63

Genes affected

RBBP6 (HGNC:9889): (RB binding protein 6, ubiquitin ligase) The retinoblastoma tumor suppressor (pRB) protein binds with many other proteins. In various human cancers, pRB suppresses cellular proliferation and is inactivated. Cell cycle-dependent phosphorylation regulates the activity of pRB. This gene encodes a protein which binds to underphosphorylated but not phosphorylated pRB. Multiple alternatively spliced transcript variants that encode different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27821404).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBBP6	NM_006910.5	c.1109T>G	p.Met370Arg	missense_variant	Exon 10 of 18	ENST00000319715.10	NP_008841.2
RBBP6	NM_018703.4	c.1109T>G	p.Met370Arg	missense_variant	Exon 10 of 17		NP_061173.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBBP6	ENST00000319715.10	c.1109T>G	p.Met370Arg	missense_variant	Exon 10 of 18	1	NM_006910.5	ENSP00000317872.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461682 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727172

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.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.54
BayesDel_addAF	Uncertain	0.039	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.20	.;T;.;.;.
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.85	D;T;D;D;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.28	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	.;L;L;.;L
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-1.6	N;N;N;.;N
REVEL	Benign	0.14
Sift	Uncertain	0.0010	D;D;D;.;D
Sift4G	Benign	0.38	T;T;D;.;T
Polyphen		0.83, 0.96	.;P;D;.;D
Vest4		0.75, 0.70, 0.77
MutPred		0.31		.;Gain of solvent accessibility (P = 0.0171);Gain of solvent accessibility (P = 0.0171);.;Gain of solvent accessibility (P = 0.0171);
MVP		0.37
MPC		0.56
ClinPred		0.67	D
GERP RS		6.0
Varity_R		0.81
gMVP		0.74

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: chr16-24573302;