19-55762699-C-T

Variant names:

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

Variant summary

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

The NM_001145014.2(RFPL4A):​c.388C>T​(p.Gln130*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000431 in 150,654 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00043 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000047 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RFPL4A NM_001145014.2 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.63

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RFPL4A	NM_001145014.2	c.388C>T	p.Gln130*	stop_gained	Exon 3 of 3	ENST00000434937.3	NP_001138486.1
RFPL4A	XM_011526915.4	c.559C>T	p.Gln187*	stop_gained	Exon 4 of 4		XP_011525217.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RFPL4A	ENST00000434937.3	c.388C>T	p.Gln130*	stop_gained	Exon 3 of 3	5	NM_001145014.2	ENSP00000392936.2

Frequencies

GnomAD3 genomes AF: 0.000432 AC: 65 AN: 150542 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000969

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00100

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000419

Gnomad FIN AF: 0.0000945

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000612

Gnomad OTH AF: 0.000974

GnomAD3 exomes AF: 0.0000579 AC: 9 AN: 155560 Hom.: 0 AF XY: 0.0000364 AC XY: 3 AN XY: 82478

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000813

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS 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: 0.0000468 AC: 65 AN: 1389878 Hom.: 0 Cov.: 71 AF XY: 0.0000467 AC XY: 32 AN XY: 685544

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000565

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000203

Gnomad4 NFE exome AF: 0.0000532

Gnomad4 OTH exome AF: 0.0000695

GnomAD4 genome AF: 0.000431 AC: 65 AN: 150654 Hom.: 0 Cov.: 33 AF XY: 0.000448 AC XY: 33 AN XY: 73698

Gnomad4 AFR AF: 0.0000967

Gnomad4 AMR AF: 0.000999

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000419

Gnomad4 FIN AF: 0.0000945

Gnomad4 NFE AF: 0.000612

Gnomad4 OTH AF: 0.000963

Alfa AF: 0.000514 Hom.: 0

ExAC AF: 0.000468 AC: 15

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.095	D
BayesDel_noAF	Benign	-0.10
CADD	Benign	22
DANN	Benign	0.95
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.019	N
Vest4		0.034
GERP RS		-3.1

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

LitVar

Other links and lift over

dbSNP: rs200829886; hg19: chr19-56274065;