5-141639532-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_173828.5(RELL2):c.386C>T(p.Ala129Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: RELL2 NM_173828.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.02

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]

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]

ACMG classification

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=0.12308261).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RELL2	NM_173828.5	c.386C>T	p.Ala129Val	missense_variant	4/7	ENST00000297164.8
FCHSD1	NM_033449.3	c.*1966G>A		3_prime_UTR_variant	20/20	ENST00000435817.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RELL2	ENST00000297164.8	c.386C>T	p.Ala129Val	missense_variant	4/7	1	NM_173828.5	P1
FCHSD1	ENST00000435817.7	c.*1966G>A		3_prime_UTR_variant	20/20	1	NM_033449.3	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 20, 2023

The c.386C>T (p.A129V) alteration is located in exon 4 (coding exon 4) of the RELL2 gene. This alteration results from a C to T substitution at nucleotide position 386, causing the alanine (A) at amino acid position 129 to be replaced by a valine (V). 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	0.15
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
Cadd	Benign	23
Dann	Uncertain	1.0
DEOGEN2	Benign	0.0022	T;.;T;.
Eigen	Benign	-0.040
Eigen_PC	Benign	0.13
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.80	T;T;.;T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.12	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.95	L;.;L;.
MutationTaster	Benign	1.0	D;D;N;N;N;N
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	0.030	N;N;N;N
REVEL	Benign	0.043
Sift	Benign	0.13	T;T;T;T
Sift4G	Benign	0.64	T;T;T;T
Polyphen		0.32	B;B;B;.
Vest4		0.26
MutPred		0.21		Loss of relative solvent accessibility (P = 0.0071);.;Loss of relative solvent accessibility (P = 0.0071);.;
MVP		0.068
MPC		0.25
ClinPred		0.28	T
GERP RS		5.7
Varity_R		0.097
gMVP		0.11

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr5-141019099;