rs3825569

Positions:

• chr14-100883961-T-A
• chr14-100883961-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001134888.3(RTL1):​c.828A>T​(p.Glu276Asp) 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.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RTL1 NM_001134888.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.81

Genes affected

RTL1 (HGNC:14665): (retrotransposon Gag like 1) This gene is a retrotransposon-derived, paternally expressed imprinted gene that is highly expressed at the late fetal stage in both the fetus and placenta. It has an overlapping maternally expressed antisense transcript, which contains several microRNAs targeting the transcripts of this gene through an RNA interference (RNAi) mechanism. This gene is essential for maintenance of the fetal capillaries. [provided by RefSeq, Jul 2009]

MIR493HG (HGNC:55978): (MIR493 cluster host gene)

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.044713974).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RTL1	NM_001134888.3	c.828A>T	p.Glu276Asp	missense_variant	4/4	ENST00000649591.1	NP_001128360.1
RTL1	XM_047431358.1	c.828A>T	p.Glu276Asp	missense_variant	3/3		XP_047287314.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RTL1	ENST00000649591.1	c.828A>T	p.Glu276Asp	missense_variant	4/4		NM_001134888.3	ENSP00000497482	P1
MIR493HG	ENST00000699458.1	n.905T>A		non_coding_transcript_exon_variant	1/6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 84

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.0090
DANN	Benign	0.85
DEOGEN2	Benign	0.049	T;T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.0076	N
LIST_S2	Benign	0.41	.;T
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.045	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.26	N;N
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.1	.;N
REVEL	Benign	0.0040
Sift	Benign	0.47	.;T
Sift4G	Benign	0.58	.;T
Vest4		0.044
MutPred		0.39		Gain of catalytic residue at L271 (P = 0.1214);Gain of catalytic residue at L271 (P = 0.1214);
MVP		0.014
MPC		0.54
ClinPred		0.041	T
GERP RS		-6.3
Varity_R		0.033
gMVP		0.43

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

LitVar

Other links and lift over

dbSNP: rs3825569; hg19: chr14-101350298;