4-37631402-T-C

Variant summary

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

The NM_001085400.2(RELL1):c.802A>G(p.Ser268Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: RELL1 NM_001085400.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.54

Genes affected

RELL1 (HGNC:27379): (RELT like 1) Involved in positive regulation of p38MAPK cascade. Located in microtubule cytoskeleton and plasma membrane. [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=0.19682613).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RELL1	NM_001085400.2	c.802A>G	p.Ser268Gly	missense_variant	6/7	ENST00000454158.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RELL1	ENST00000454158.7	c.802A>G	p.Ser268Gly	missense_variant	6/7	5	NM_001085400.2	P1
RELL1	ENST00000314117.8	c.802A>G	p.Ser268Gly	missense_variant	6/7	1		P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

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

Mar 07, 2024

The c.802A>G (p.S268G) alteration is located in exon 6 (coding exon 6) of the RELL1 gene. This alteration results from a A to G substitution at nucleotide position 802, causing the serine (S) at amino acid position 268 to be replaced by a glycine (G). 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	0.074
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
Cadd	Benign	18
Dann	Uncertain	0.98
DEOGEN2	Benign	0.012	T;T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.62	D
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.20	T;T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	1.9	M;M
MutationTaster	Benign	0.65	D;D
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.6	N;N
REVEL	Benign	0.075
Sift	Pathogenic	0.0	D;D
Sift4G	Uncertain	0.011	D;D
Polyphen		0.73	P;P
Vest4		0.33
MutPred		0.16		Gain of glycosylation at T270 (P = 0.0172);Gain of glycosylation at T270 (P = 0.0172);
MVP		0.043
MPC		0.76
ClinPred		0.80	D
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.14
gMVP		0.19

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-37633024;