19-55763083-C-G

Variant names:

• chr19-55763083-C-G
• rs751034639
• NM_001145014.2:c.772C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001145014.2(RFPL4A):​c.772C>G​(p.Arg258Gly) variant causes a missense 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. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R258C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RFPL4A NM_001145014.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.789
• Publications: 0 publications found

Genes affected

RFPL4A (HGNC:16449): (ret finger protein like 4A) Predicted to enable ubiquitin-protein transferase activity. Predicted to be involved in positive regulation of transcription, DNA-templated. Predicted to be located in nucleus. Predicted to be active in chromatin and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.087825805).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145014.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RFPL4A	NM_001145014.2	MANE Select	c.772C>G	p.Arg258Gly	missense	Exon 3 of 3	NP_001138486.1	A6NLU0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RFPL4A	ENST00000434937.3	TSL:5 MANE Select	c.772C>G	p.Arg258Gly	missense	Exon 3 of 3	ENSP00000392936.2	A6NLU0
	RFPL4A	ENST00000897443.1		c.772C>G	p.Arg258Gly	missense	Exon 2 of 2	ENSP00000567502.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1399324 Hom.: 0 Cov.: 97 AF XY: 0.00 AC XY: 0 AN XY: 690190

African (AFR) AF: 0.00 AC: 0 AN: 31562

American (AMR) AF: 0.00 AC: 0 AN: 35672

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25176

East Asian (EAS) AF: 0.00 AC: 0 AN: 35738

South Asian (SAS) AF: 0.00 AC: 0 AN: 79204

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49390

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5688

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078834

Other (OTH) AF: 0.00 AC: 0 AN: 58060

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	0.99
DANN	Benign	0.28
DEOGEN2	Benign	0.011	T
Eigen	Benign	-2.1
Eigen_PC	Benign	-2.2
FATHMM_MKL	Benign	0.0081	N
LIST_S2	Benign	0.24	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.088	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.42	N
PhyloP100		-0.79
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.46	N
REVEL	Benign	0.084
Sift	Benign	0.35	T
Sift4G	Benign	0.33	T
Polyphen		0.041	B
Vest4		0.13
MutPred		0.46		Gain of sheet (P = 0.0827)
MVP		0.072
MPC		1.2
ClinPred		0.13	T
GERP RS		-5.6
Varity_R		0.26
gMVP		0.20
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs751034639; hg19: chr19-56274449;