chr19-55762699-C-A

Variant names:

• chr19-55762699-C-A
• rs200829886
• NM_001145014.2:c.388C>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001145014.2(RFPL4A):​c.388C>A​(p.Gln130Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000057 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RFPL4A NM_001145014.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.63
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.04855156).

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.388C>A	p.Gln130Lys	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.388C>A	p.Gln130Lys	missense	Exon 3 of 3	ENSP00000392936.2	A6NLU0
	RFPL4A	ENST00000897443.1		c.388C>A	p.Gln130Lys	missense	Exon 2 of 2	ENSP00000567502.1

Frequencies

GnomAD3 genomes AF: 0.0000265 AC: 4 AN: 151068 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000726

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000484

GnomAD2 exomes AF: 0.00 AC: 0 AN: 155560 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000574 AC: 8 AN: 1394362 Hom.: 0 Cov.: 71 AF XY: 0.00000872 AC XY: 6 AN XY: 687782

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000190 AC: 6 AN: 31568

American (AMR) AF: 0.0000281 AC: 1 AN: 35580

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25156

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 79174

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49240

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5682

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1074416

Other (OTH) AF: 0.0000173 AC: 1 AN: 57808

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000265 AC: 4 AN: 151068 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 73802

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000726 AC: 3 AN: 41294

American (AMR) AF: 0.00 AC: 0 AN: 15118

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4778

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67356

Other (OTH) AF: 0.000484 AC: 1 AN: 2064

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000000000130562), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.15
DANN	Benign	0.43
DEOGEN2	Benign	0.0096	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0031	N
LIST_S2	Benign	0.050	T
M_CAP	Benign	0.0013	T
MetaRNN	Benign	0.049	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.080	N
PhyloP100		-2.6
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.45	N
REVEL	Benign	0.0080
Sift	Benign	0.31	T
Sift4G	Benign	0.31	T
Polyphen		0.076	B
Vest4		0.059
MutPred		0.39		Gain of methylation at Q130 (P = 0.0053)
MVP		0.030
MPC		1.0
ClinPred		0.057	T
GERP RS		-3.1
Varity_R		0.10
gMVP		0.10
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs200829886; hg19: chr19-56274065;