Variant chr11-66625174-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_006328.4(RBM14):c.1298T>C(p.Val433Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000217 in 1,612,292 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

RBM14
NM_006328.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.81

Variant links:

Genes affected

RBM14 (HGNC:14219): (RNA binding motif protein 14) This gene encodes a ribonucleoprotein that functions as a general nuclear coactivator, and an RNA splicing modulator. This protein contains two RNA recognition motifs (RRM) at the N-terminus, and multiple hexapeptide repeat domain at the C-terminus that interacts with thyroid hormone receptor-binding protein (TRBP), and is required for transcription activation. Alternatively spliced transcript variants encoding different isoforms (with opposing effects on transcription) have been described for this gene. [provided by RefSeq, Oct 2011]

RBM14 links:

RBM14-RBM4 (HGNC:):

RBM14-RBM4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.098048896).

BS2

High AC in GnomAdExome4 at 33 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBM14	NM_006328.4 linkuse as main transcript	c.1298T>C	p.Val433Ala	missense_variant	2/3	ENST00000310137.5	NP_006319.1
RBM14-RBM4	NM_001198845.2 linkuse as main transcript	c.337+8117T>C		intron_variant			NP_001185774.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBM14	ENST00000310137.5 linkuse as main transcript	c.1298T>C	p.Val433Ala	missense_variant	2/3	1	NM_006328.4	ENSP00000311747	P3	Q96PK6-1
RBM14	ENST00000393979.3 linkuse as main transcript	c.448+850T>C		intron_variant		1		ENSP00000377548	A1	Q96PK6-2
RBM14	ENST00000409738.4 linkuse as main transcript	c.338-1287T>C		intron_variant		1		ENSP00000386995		Q96PK6-4

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152054

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000226

AC:

AN:

1460238

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

726482

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000270

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000132

AC:

AN:

152054

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74268

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.00000756

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 26, 2024

The c.1298T>C (p.V433A) alteration is located in exon 2 (coding exon 2) of the RBM14 gene. This alteration results from a T to C substitution at nucleotide position 1298, causing the valine (V) at amino acid position 433 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

0.10

BayesDel_addAF

Uncertain

0.048

BayesDel_noAF

Benign

-0.17

CADD

Benign

DANN

Benign

0.83

DEOGEN2

Benign

0.056

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.016

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.76

M_CAP

Benign

0.022

MetaRNN

Benign

0.098

MetaSVM

Benign

-0.80

MutationAssessor

Benign

0.20

MutationTaster

Benign

1.0

D;D;N;D;D;D

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-0.36

REVEL

Uncertain

0.30

Sift

Benign

0.10

Sift4G

Benign

1.0

Polyphen

0.048

Vest4

0.22

MutPred

0.19

Gain of helix (P = 0.0128);

MVP

0.082

MPC

0.16

ClinPred

0.12

GERP RS

4.6

Varity_R

0.054

gMVP

0.48

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over