12-88046899-G-T

Variant names:

• chr12-88046899-G-T
• rs9262
• NM_001009894.3:c.712G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001009894.3(RLIG1):​c.712G>T​(p.Val238Leu) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Benign in ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: RLIG1 NM_001009894.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16
• Publications: 0 publications found

Genes affected

RLIG1 (HGNC:25322): (RNA 5'-phosphate and 3'-OH ligase 1) Predicted to act upstream of or within hematopoietic progenitor cell differentiation. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.020855725).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RLIG1	NM_001009894.3	c.712G>T	p.Val238Leu	missense_variant	Exon 6 of 7	ENST00000356891.4	NP_001009894.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RLIG1	ENST00000356891.4	c.712G>T	p.Val238Leu	missense_variant	Exon 6 of 7	1	NM_001009894.3	ENSP00000349358.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 39

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.046
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.50
DANN	Benign	0.73
DEOGEN2	Benign	0.017	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.21	T
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.021	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-1.4	N
PhyloP100		-1.2
PROVEAN	Benign	0.97	N
REVEL	Benign	0.038
Sift	Benign	0.56	T
Sift4G	Benign	0.46	T
Polyphen		0.0	B
Vest4		0.055
MutPred		0.082		Gain of catalytic residue at V238 (P = 0.011);
MVP		0.061
MPC		0.20
ClinPred		0.036	T
GERP RS		-4.2
Varity_R		0.020
gMVP		0.35
Mutation Taster		=98/2	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: rs9262; hg19: chr12-88440676;