6-42886421-A-C

Variant names:

• chr6-42886421-A-C
• rs370265415
• NM_001366481.3:c.725A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001366481.3(RPL7L1):​c.725A>C​(p.Tyr242Ser) 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. 11/18 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. Y242C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RPL7L1 NM_001366481.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.377
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14570737).

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.725A>C	p.Tyr242Ser	missense	Exon 6 of 6	NP_001353410.1	Q6DKI1-1
	RPL7L1	NM_198486.5		c.725A>C	p.Tyr242Ser	missense	Exon 6 of 7	NP_940888.3	Q6DKI1-1
	RPL7L1	NR_134562.3		n.1136A>C		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.725A>C	p.Tyr242Ser	missense	Exon 6 of 6	ENSP00000418221.3	Q6DKI1-1
	RPL7L1	ENST00000304734.9	TSL:1	c.725A>C	p.Tyr242Ser	missense	Exon 6 of 7	ENSP00000346063.4	Q6DKI1-1
	RPL7L1	ENST00000397415.7	TSL:1	n.1113A>C		non_coding_transcript_exon	Exon 6 of 6

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD2 exomes AF: 0.00000423 AC: 1 AN: 236382 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000903

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.94e-7 AC: 1 AN: 1440328 Hom.: 0 Cov.: 28 AF XY: 0.00000139 AC XY: 1 AN XY: 717248

African (AFR) AF: 0.00 AC: 0 AN: 33282

American (AMR) AF: 0.00 AC: 0 AN: 44648

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26100

East Asian (EAS) AF: 0.00 AC: 0 AN: 39664

South Asian (SAS) AF: 0.00 AC: 0 AN: 86048

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39384

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4122

European-Non Finnish (NFE) AF: 9.03e-7 AC: 1 AN: 1107160

Other (OTH) AF: 0.00 AC: 0 AN: 59920

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Uncertain	0.039	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	19
DANN	Benign	0.94
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.10
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.84	T
PhyloP100		0.38
PrimateAI	Uncertain	0.51	T
REVEL	Benign	0.16
MVP		0.59
MPC		0.47
ClinPred		0.21	T
GERP RS		5.4
gMVP		0.71
Mutation Taster		=86/14	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: rs370265415; hg19: chr6-42854159;