6-112349792-C-G

Variant names:

• chr6-112349792-C-G
• NM_001013734.3:c.84C>G
• RFPL4B p.His28Gln

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001013734.3(RFPL4B):​c.84C>G​(p.His28Gln) 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 pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RFPL4B NM_001013734.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.143
• Publications: 0 publications found

Genes affected

RFPL4B (HGNC:33264): (ret finger protein like 4B) Predicted to enable metal ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000281613 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001013734.3. 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
	RFPL4B	NM_001013734.3	MANE Select	c.84C>G	p.His28Gln	missense	Exon 3 of 3	NP_001013756.2	Q6ZWI9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RFPL4B	ENST00000441065.3	TSL:2 MANE Select	c.84C>G	p.His28Gln	missense	Exon 3 of 3	ENSP00000423391.1	Q6ZWI9
	ENSG00000281613	ENST00000587816.2	TSL:5	c.84C>G	p.His28Gln	missense	Exon 5 of 5	ENSP00000487146.1	A0A0D9SG52
	RFPL4B	ENST00000962225.1		c.84C>G	p.His28Gln	missense	Exon 2 of 2	ENSP00000632284.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.61
BayesDel_addAF	Uncertain	0.072	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	23
DANN	Benign	0.87
DEOGEN2	Benign	0.18	T
Eigen	Benign	-0.63
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.060	N
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.0063	T
MetaRNN	Pathogenic	0.95	D
MetaSVM	Benign	-0.92	T
MutationAssessor	Pathogenic	4.1	H
PhyloP100		-0.14
PrimateAI	Benign	0.40	T
PROVEAN	Pathogenic	-5.3	D
REVEL	Uncertain	0.33
Sift	Benign	0.24	T
Sift4G	Pathogenic	0.0	D
Varity_R		0.15
gMVP		0.60
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.82		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.82		Position offset: 1

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr6-112670994;