Genetic Variant RFPL4B:p.Ser23Ala (chr6-112349775-T-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001013734.3(RFPL4B):c.67T>G(p.Ser23Ala) 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

RFPL4B
NM_001013734.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.269

Publications

0 publications found

Variant links:

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]

RFPL4B links:

ENSG00000281613 (HGNC:):

ENSG00000281613 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20468664).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RFPL4B	NM_001013734.3 link	c.67T>G	p.Ser23Ala	missense_variant	Exon 3 of 3	ENST00000441065.3	NP_001013756.2	Q6ZWI9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
RFPL4B	ENST00000441065.3 link	c.67T>G	p.Ser23Ala	missense_variant	Exon 3 of 3	2	NM_001013734.3	ENSP00000423391.1	Q6ZWI9
ENSG00000281613	ENST00000587816.2 link	c.67T>G	p.Ser23Ala	missense_variant	Exon 5 of 5	5		ENSP00000487146.1	A0A0D9SG52
ENSG00000281613	ENST00000585611.5 link	c.67T>G	p.Ser23Ala	missense_variant	Exon 5 of 5	5		ENSP00000486440.1	A0A0D9SFB2
ENSG00000281613	ENST00000590673.5 link	c.67T>G	p.Ser23Ala	missense_variant	Exon 4 of 4	5		ENSP00000486934.1	A0A0D9SFW1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251468

AF XY:

0.00

show subpopulations

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:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 27, 2021

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.67T>G (p.S23A) alteration is located in exon 3 (coding exon 1) of the RFPL4B gene. This alteration results from a T to G substitution at nucleotide position 67, causing the serine (S) at amino acid position 23 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.71

CADD

Benign

6.5

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.013

.;.;.;T

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.036

LIST_S2

Benign

0.23

T;T;T;T

M_CAP

Benign

0.0025

MetaRNN

Benign

0.20

T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.4

.;.;.;L

PhyloP100

-0.27

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.8

.;.;.;N

REVEL

Benign

0.057

Sift

Benign

0.075

.;.;.;T

Sift4G

Benign

0.31

T;T;T;T

Polyphen

0.83

.;.;.;P

Vest4

0.057

MutPred

0.50

Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);

MVP

0.072

MPC

0.18

ClinPred

0.28

GERP RS

2.9

Varity_R

0.078

gMVP

0.10

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over