chr5-141639588-C-T

Variant names:

• chr5-141639588-C-T
• rs139840036
• NM_173828.5:c.442C>T

Variant summary

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

The NM_173828.5(RELL2):​c.442C>T​(p.Arg148Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000979 in 1,613,870 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00010 (0 hom.)
• Consequence: RELL2 NM_173828.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.962
• Publications: 3 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.

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.442C>T	p.Arg148Cys	missense	Exon 4 of 7	NP_776189.3
	FCHSD1	NM_033449.3	MANE Select	c.*1910G>A		3_prime_UTR	Exon 20 of 20	NP_258260.1	Q86WN1-1
	RELL2	NM_001130029.2		c.442C>T	p.Arg148Cys	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.442C>T	p.Arg148Cys	missense	Exon 4 of 7	ENSP00000297164.3	Q8NC24
	RELL2	ENST00000444782.5	TSL:1	c.442C>T	p.Arg148Cys	missense	Exon 5 of 8	ENSP00000409443.1	Q8NC24
	FCHSD1	ENST00000435817.7	TSL:1 MANE Select	c.*1910G>A		3_prime_UTR	Exon 20 of 20	ENSP00000399259.2	Q86WN1-1

Frequencies

GnomAD3 genomes AF: 0.0000657 AC: 10 AN: 152134 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

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: 0.000132

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000882 AC: 22 AN: 249310 AF XY: 0.0000741

Gnomad AFR exome AF: 0.0000618

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000161

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000101 AC: 148 AN: 1461736 Hom.: 0 Cov.: 34 AF XY: 0.000116 AC XY: 84 AN XY: 727164

African (AFR) AF: 0.0000597 AC: 2 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39700

South Asian (SAS) AF: 0.0000812 AC: 7 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53348

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5730

European-Non Finnish (NFE) AF: 0.000122 AC: 136 AN: 1111986

Other (OTH) AF: 0.0000166 AC: 1 AN: 60386

GnomAD4 genome AF: 0.0000657 AC: 10 AN: 152134 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74310

African (AFR) AF: 0.0000241 AC: 1 AN: 41432

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.000185 Hom.: 0

Bravo AF: 0.0000756

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.0000906 AC: 11

EpiCase AF: 0.000164

EpiControl AF: 0.000178

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	Pathogenic	0.57
BayesDel_addAF	Benign	-0.013	T
BayesDel_noAF	Uncertain	0.0
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.090	T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Benign	0.73	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.059	D
MetaRNN	Uncertain	0.53	D
MetaSVM	Benign	-0.83	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		0.96
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-4.0	D
REVEL	Benign	0.22
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.68
MVP		0.24
MPC		0.84
ClinPred		0.68	D
GERP RS		4.5
Varity_R		0.38
gMVP		0.34
Mutation Taster		=53/47	polymorphism

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

Other links and lift over

dbSNP: rs139840036; hg19: chr5-141019155; COSMIC: COSV51836855; COSMIC: COSV51836855;