4-37634996-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001085400.2(RELL1):c.571G>A(p.Val191Met) 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. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V191E) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: RELL1 NM_001085400.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.07

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27543545).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RELL1	NM_001085400.2	c.571G>A	p.Val191Met	missense_variant	5/7	ENST00000454158.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RELL1	ENST00000454158.7	c.571G>A	p.Val191Met	missense_variant	5/7	5	NM_001085400.2	P1
RELL1	ENST00000314117.8	c.571G>A	p.Val191Met	missense_variant	5/7	1		P1
RELL1	ENST00000512114.1	c.634G>A	p.Val212Met	missense_variant	5/5	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

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

Feb 03, 2022

The c.571G>A (p.V191M) alteration is located in exon 5 (coding exon 5) of the RELL1 gene. This alteration results from a G to A substitution at nucleotide position 571, causing the valine (V) at amino acid position 191 to be replaced by a methionine (M). 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	0.20
BayesDel_addAF	Uncertain	0.028	T
BayesDel_noAF	Benign	-0.20
Cadd	Uncertain	24
Dann	Uncertain	1.0
DEOGEN2	Benign	0.021	T;T;.
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.88	D
M_CAP	Benign	0.0086	T
MetaRNN	Benign	0.28	T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.2	M;M;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-0.93	N;N;N
REVEL	Benign	0.086
Sift	Benign	0.063	T;T;D
Sift4G	Benign	0.082	T;T;.
Polyphen		0.85	P;P;.
Vest4		0.67
MutPred		0.36		Gain of catalytic residue at V187 (P = 0.0332);Gain of catalytic residue at V187 (P = 0.0332);.;
MVP		0.30
MPC		0.87
ClinPred		0.82	D
GERP RS		5.2
Varity_R		0.066
gMVP		0.32

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: chr4-37636618;