rs1766270243

Variant names:

• chr6-42886409-G-A
• rs1766270243
• NM_001366481.3:c.713G>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001366481.3(RPL7L1):​c.713G>A​(p.Gly238Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: RPL7L1 NM_001366481.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.13
• Publications: 0 publications found

Genes affected

RPL7L1 (HGNC:21370): (ribosomal protein L7 like 1) Enables RNA binding activity. Predicted to be involved in maturation of LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA). Predicted to act upstream of or within blastocyst formation. Predicted to be located in nucleolus. Predicted to be part of cytosolic large ribosomal subunit. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.923

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001366481.3. 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
	RPL7L1	NM_001366481.3	MANE Select	c.713G>A	p.Gly238Asp	missense	Exon 6 of 6	NP_001353410.1	Q6DKI1-1
	RPL7L1	NM_198486.5		c.713G>A	p.Gly238Asp	missense	Exon 6 of 7	NP_940888.3	Q6DKI1-1
	RPL7L1	NR_134562.3		n.1124G>A		non_coding_transcript_exon	Exon 6 of 7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPL7L1	ENST00000493763.7	TSL:1 MANE Select	c.713G>A	p.Gly238Asp	missense	Exon 6 of 6	ENSP00000418221.3	Q6DKI1-1
	RPL7L1	ENST00000304734.9	TSL:1	c.713G>A	p.Gly238Asp	missense	Exon 6 of 7	ENSP00000346063.4	Q6DKI1-1
	RPL7L1	ENST00000397415.7	TSL:1	n.1101G>A		non_coding_transcript_exon	Exon 6 of 6

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 0

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	Pathogenic	0.75
BayesDel_addAF	Pathogenic	0.50	D
BayesDel_noAF	Pathogenic	0.49
CADD	Pathogenic	32
DANN	Uncertain	1.0
Eigen	Pathogenic	1.0
Eigen_PC	Pathogenic	0.95
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.027	D
MetaRNN	Pathogenic	0.92	D
MetaSVM	Uncertain	0.29	D
PhyloP100		9.1
PrimateAI	Uncertain	0.75	T
REVEL	Pathogenic	0.81
MVP		0.89
MPC		1.2
ClinPred		1.0	D
GERP RS		5.4
gMVP		0.91
Mutation Taster		=17/83	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs1766270243; hg19: chr6-42854147;