5-141639596-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_173828.5(RELL2):c.450G>T(p.Lys150Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000126 in 1,613,762 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

RELL2
NM_173828.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.670

Variant links:

Genes affected

RELL2 (HGNC:26902): (RELT like 2) Predicted to enable collagen binding activity. Involved in positive regulation of p38MAPK cascade. Predicted to be located in extracellular matrix. [provided by Alliance of Genome Resources, Apr 2022]

RELL2 links:

FCHSD1 (HGNC:25463): (FCH and double SH3 domains 1) Predicted to enable lipid binding activity. Predicted to be involved in neuromuscular synaptic transmission and positive regulation of actin filament polymerization. Predicted to be located in cell projection and perikaryon. Predicted to be active in neuromuscular junction and recycling endosome. Predicted to colocalize with cuticular plate. [provided by Alliance of Genome Resources, Apr 2022]

FCHSD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.22754997).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RELL2	NM_173828.5 linkuse as main transcript	c.450G>T	p.Lys150Asn	missense_variant	4/7	ENST00000297164.8
FCHSD1	NM_033449.3 linkuse as main transcript	c.*1902C>A		3_prime_UTR_variant	20/20	ENST00000435817.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RELL2	ENST00000297164.8 linkuse as main transcript	c.450G>T	p.Lys150Asn	missense_variant	4/7	1	NM_173828.5	P1
FCHSD1	ENST00000435817.7 linkuse as main transcript	c.*1902C>A		3_prime_UTR_variant	20/20	1	NM_033449.3	P1	Q86WN1-1

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152122

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:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000642

AC:

AN:

249212

Hom.:

AF XY:

0.0000667

AC XY:

AN XY:

135002

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000143

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000135

AC:

198

AN:

1461640

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

727106

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

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:

0.000187

Gnomad4 NFE exome

AF:

0.000165

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152122

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74308

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:

0.0000942

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000140

Hom.:

Bravo

AF:

0.0000491

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000519

AC:

ExAC

AF:

0.0000577

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.00

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

May 23, 2023

The c.450G>T (p.K150N) alteration is located in exon 4 (coding exon 4) of the RELL2 gene. This alteration results from a G to T substitution at nucleotide position 450, causing the lysine (K) at amino acid position 150 to be replaced by an asparagine (N). 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

Pathogenic

0.96

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.36

Cadd

Uncertain

Dann

Uncertain

1.0

DEOGEN2

Benign

0.15

T;.;T;.

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.86

D;D;.;D

M_CAP

Benign

0.022

MetaRNN

Benign

0.23

T;T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Uncertain

2.6

M;.;M;.

MutationTaster

Benign

1.0

D;D;D;D;D;D

PrimateAI

Uncertain

0.73

PROVEAN

Uncertain

-3.1

D;D;D;D

REVEL

Benign

0.14

Sift

Uncertain

0.0040

D;D;D;D

Sift4G

Uncertain

0.013

D;D;D;D

Polyphen

1.0

D;D;D;.

Vest4

0.46

MutPred

0.21

Loss of ubiquitination at K150 (P = 0.0297);.;Loss of ubiquitination at K150 (P = 0.0297);.;

MVP

0.13

MPC

0.47

ClinPred

0.52

GERP RS

1.1

Varity_R

0.28

gMVP

0.22

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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