5-141639532-C-T

Variant names:

• chr5-141639532-C-T
• NM_173828.5:c.386C>T

Variant summary

Our verdict is Uncertain significance. The variant received 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. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: RELL2 NM_173828.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.02
• Publications: 0 publications found

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

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=0.12308261).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173828.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RELL2	NM_173828.5	MANE Select	c.386C>T	p.Ala129Val	missense	Exon 4 of 7	NP_776189.3
	FCHSD1	NM_033449.3	MANE Select	c.*1966G>A		3_prime_UTR	Exon 20 of 20	NP_258260.1	Q86WN1-1
	RELL2	NM_001130029.2		c.386C>T	p.Ala129Val	missense	Exon 5 of 8	NP_001123501.1	Q8NC24

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RELL2	ENST00000297164.8	TSL:1 MANE Select	c.386C>T	p.Ala129Val	missense	Exon 4 of 7	ENSP00000297164.3	Q8NC24
	RELL2	ENST00000444782.5	TSL:1	c.386C>T	p.Ala129Val	missense	Exon 5 of 8	ENSP00000409443.1	Q8NC24
	FCHSD1	ENST00000435817.7	TSL:1 MANE Select	c.*1966G>A		3_prime_UTR	Exon 20 of 20	ENSP00000399259.2	Q86WN1-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-0.040
Eigen_PC	Benign	0.13
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.95	L
PhyloP100		5.0
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	0.030	N
REVEL	Benign	0.043
Sift	Benign	0.13	T
Sift4G	Benign	0.64	T
Polyphen		0.32	B
Vest4		0.26
MutPred		0.21		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
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

hg19: chr5-141019099;