20-62412663-G-A

Variant names:

• chr20-62412663-G-A
• NM_080833.3:c.1837C>T

Variant summary

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

The NM_080833.3(RBBP8NL):​c.1837C>T​(p.Pro613Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,426 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: RBBP8NL NM_080833.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.23

Genes affected

RBBP8NL (HGNC:16144): (RBBP8 N-terminal like) Located in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

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=0.069429636).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBBP8NL	NM_080833.3	c.1837C>T	p.Pro613Ser	missense_variant	Exon 13 of 14	ENST00000252998.2	NP_543023.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBBP8NL	ENST00000252998.2	c.1837C>T	p.Pro613Ser	missense_variant	Exon 13 of 14	2	NM_080833.3	ENSP00000252998.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455426 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 724330

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

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 10, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1837C>T (p.P613S) alteration is located in exon 13 (coding exon 12) of the RBBP8NL gene. This alteration results from a C to T substitution at nucleotide position 1837, causing the proline (P) at amino acid position 613 to be replaced by a serine (S). 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	Benign	0.076
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	7.8
DANN	Benign	0.57
DEOGEN2	Benign	0.0048	T
Eigen	Benign	-0.93
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.069	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.4	L
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.070	N
REVEL	Benign	0.0040
Sift	Benign	0.080	T
Sift4G	Benign	0.42	T
Polyphen		0.13	B
Vest4		0.15
MutPred		0.30		Gain of phosphorylation at P613 (P = 0.0068);
MVP		0.088
MPC		0.070
ClinPred		0.068	T
GERP RS		2.3
Varity_R		0.026
gMVP		0.027

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: chr20-60987719;