rs776691999

Variant names:

• chr19-55762739-C-A
• rs776691999
• NM_001145014.2:c.428C>A

Your query was ambiguous. Multiple possible variants found:

• chr19-55762739-C-A
• chr19-55762739-C-T

Variant summary

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

The NM_001145014.2(RFPL4A):​c.428C>A​(p.Thr143Asn) 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 0.000033 (0 hom., cov: 27)
  • Exomes 𝑓: 0.000074 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RFPL4A NM_001145014.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.30
• 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=0.040818453).

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.428C>A	p.Thr143Asn	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.428C>A	p.Thr143Asn	missense	Exon 3 of 3	ENSP00000392936.2	A6NLU0
	RFPL4A	ENST00000897443.1		c.428C>A	p.Thr143Asn	missense	Exon 2 of 2	ENSP00000567502.1

Frequencies

GnomAD3 genomes AF: 0.0000265 AC: 4 AN: 150762 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000866

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000212

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000174 AC: 27 AN: 155396 AF XY: 0.000145

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00201

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000117

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000743 AC: 104 AN: 1399066 Hom.: 0 Cov.: 60 AF XY: 0.0000768 AC XY: 53 AN XY: 690040

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

African (AFR) AF: 0.0000633 AC: 2 AN: 31584

American (AMR) AF: 0.00 AC: 0 AN: 35696

Ashkenazi Jewish (ASJ) AF: 0.00143 AC: 36 AN: 25176

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

South Asian (SAS) AF: 0.000366 AC: 29 AN: 79220

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49274

Middle Eastern (MID) AF: 0.000527 AC: 3 AN: 5692

European-Non Finnish (NFE) AF: 0.0000232 AC: 25 AN: 1078706

Other (OTH) AF: 0.000155 AC: 9 AN: 57980

⚠️ 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: 0.0000331 AC: 5 AN: 150882 Hom.: 0 Cov.: 27 AF XY: 0.0000678 AC XY: 5 AN XY: 73730

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

African (AFR) AF: 0.00 AC: 0 AN: 41046

American (AMR) AF: 0.00 AC: 0 AN: 15150

Ashkenazi Jewish (ASJ) AF: 0.000866 AC: 3 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.000423 AC: 2 AN: 4724

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10472

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67586

Other (OTH) AF: 0.00 AC: 0 AN: 2080

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0634128), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.000434 Hom.: 0

ExAC AF: 0.000226 AC: 7

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	0.10
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	15
DANN	Benign	0.82
DEOGEN2	Benign	0.020	T
Eigen	Benign	-0.99
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.22	T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.041	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.7	L
PhyloP100		-1.3
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.013
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.015	D
Polyphen		0.086	B
Vest4		0.087
MutPred		0.42		Loss of phosphorylation at T143 (P = 0.0418)
MVP		0.030
MPC		1.0
ClinPred		0.026	T
GERP RS		1.6
Varity_R		0.17
gMVP		0.067
Mutation Taster		=89/11	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: rs776691999; hg19: chr19-56274105;