6-112349745-G-A

Position:

• chr6-112349745-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_001013734.3(RFPL4B):​c.37G>A​(p.Val13Ile) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: RFPL4B NM_001013734.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.75

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0942134).
• BP6: Variant 6-112349745-G-A is Benign according to our data. Variant chr6-112349745-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2548807.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RFPL4B	NM_001013734.3	c.37G>A	p.Val13Ile	missense_variant	3/3	ENST00000441065.3	NP_001013756.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RFPL4B	ENST00000441065.3	c.37G>A	p.Val13Ile	missense_variant	3/3	2	NM_001013734.3	ENSP00000423391	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 18, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.014
DANN	Benign	0.57
DEOGEN2	Benign	0.0019	.;.;.;T
Eigen	Benign	-2.0
Eigen_PC	Benign	-2.1
FATHMM_MKL	Benign	0.0043	N
LIST_S2	Benign	0.42	T;T;D;D
M_CAP	Benign	0.0013	T
MetaRNN	Benign	0.094	T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.91	.;.;.;N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.080	.;.;.;N
REVEL	Benign	0.028
Sift	Benign	0.55	.;.;.;T
Sift4G	Benign	0.49	T;T;T;T
Polyphen		0.0040	.;.;.;B
Vest4		0.043
MutPred		0.45		Loss of catalytic residue at V13 (P = 0.0445);Loss of catalytic residue at V13 (P = 0.0445);Loss of catalytic residue at V13 (P = 0.0445);Loss of catalytic residue at V13 (P = 0.0445);
MVP		0.030
MPC		0.10
ClinPred		0.050	T
GERP RS		-8.3
Varity_R		0.020
gMVP		0.17

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-112670947;