4-37635055-G-A

Variant summary

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

The NM_001085400.2(RELL1):c.512C>T(p.Pro171Leu) 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. Variant has been reported in ClinVar 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: 5.12

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=0.32366696).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RELL1	NM_001085400.2	c.512C>T	p.Pro171Leu	missense_variant	5/7	ENST00000454158.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RELL1	ENST00000454158.7	c.512C>T	p.Pro171Leu	missense_variant	5/7	5	NM_001085400.2	P1
RELL1	ENST00000314117.8	c.512C>T	p.Pro171Leu	missense_variant	5/7	1		P1
RELL1	ENST00000512114.1	c.575C>T	p.Pro192Leu	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

Nov 08, 2022

The c.512C>T (p.P171L) alteration is located in exon 5 (coding exon 5) of the RELL1 gene. This alteration results from a C to T substitution at nucleotide position 512, causing the proline (P) at amino acid position 171 to be replaced by a leucine (L). 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	0.12
BayesDel_addAF	Benign	0.0084	T
BayesDel_noAF	Benign	-0.23
Cadd	Uncertain	23
Dann	Uncertain	1.0
DEOGEN2	Benign	0.11	T;T;.
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Uncertain	0.96	D
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.32	T;T;T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	1.6	L;L;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.65	T
PROVEAN	Pathogenic	-4.5	D;D;D
REVEL	Benign	0.20
Sift	Uncertain	0.0050	D;D;D
Sift4G	Benign	0.23	T;T;.
Polyphen		1.0	D;D;.
Vest4		0.55
MutPred		0.16		Loss of glycosylation at K173 (P = 0.0152);Loss of glycosylation at K173 (P = 0.0152);.;
MVP		0.16
MPC		0.60
ClinPred		0.88	D
GERP RS		6.0
Varity_R		0.19
gMVP		0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1577578780; hg19: chr4-37636677;