5-141640005-G-T

Variant names:

• chr5-141640005-G-T
• rs146298065
• NM_173828.5:c.589G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_173828.5(RELL2):​c.589G>T​(p.Gly197Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0004 in 1,613,504 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 0.00024 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00042 (0 hom.)
• Consequence: RELL2 NM_173828.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.14
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.17866644).

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.589G>T	p.Gly197Trp	missense	Exon 5 of 7	NP_776189.3
	FCHSD1	NM_033449.3	MANE Select	c.*1493C>A		3_prime_UTR	Exon 20 of 20	NP_258260.1	Q86WN1-1
	RELL2	NM_001130029.2		c.589G>T	p.Gly197Trp	missense	Exon 6 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.589G>T	p.Gly197Trp	missense	Exon 5 of 7	ENSP00000297164.3	Q8NC24
	RELL2	ENST00000444782.5	TSL:1	c.589G>T	p.Gly197Trp	missense	Exon 6 of 8	ENSP00000409443.1	Q8NC24
	FCHSD1	ENST00000435817.7	TSL:1 MANE Select	c.*1493C>A		3_prime_UTR	Exon 20 of 20	ENSP00000399259.2	Q86WN1-1

Frequencies

GnomAD3 genomes AF: 0.000237 AC: 36 AN: 152196 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000482

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: 0.000485

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000198 AC: 49 AN: 246914 AF XY: 0.000201

Gnomad AFR exome AF: 0.0000639

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000100

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000924

Gnomad NFE exome AF: 0.000391

Gnomad OTH exome AF: 0.000329

GnomAD4 exome AF: 0.000417 AC: 609 AN: 1461308 Hom.: 0 Cov.: 35 AF XY: 0.000399 AC XY: 290 AN XY: 726968

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

American (AMR) AF: 0.0000224 AC: 1 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.0000188 AC: 1 AN: 53112

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.000528 AC: 587 AN: 1111766

Other (OTH) AF: 0.000282 AC: 17 AN: 60384

GnomAD4 genome AF: 0.000237 AC: 36 AN: 152196 Hom.: 0 Cov.: 33 AF XY: 0.000215 AC XY: 16 AN XY: 74338

African (AFR) AF: 0.0000482 AC: 2 AN: 41464

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

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

European-Non Finnish (NFE) AF: 0.000485 AC: 33 AN: 68020

Other (OTH) AF: 0.000478 AC: 1 AN: 2094

Alfa AF: 0.000274 Hom.: 0

Bravo AF: 0.000249

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.000181 AC: 22

EpiCase AF: 0.00104

EpiControl AF: 0.000771

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	0.19
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0072	T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		4.1
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.11
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.028	D
Polyphen		0.96	D
Vest4		0.49
MVP		0.043
MPC		0.83
ClinPred		0.22	T
GERP RS		5.3
Varity_R		0.21
gMVP		0.17
Mutation Taster		=91/9	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: rs146298065; hg19: chr5-141019572;